Developed Liver Failure Research Articles

Neural Network System for Diagnosing Liver Failure in Surgery

Clinical decision support systems are rapidly developing along with digital technologies nowadays. Neural network methods have become more common in solving practical problems in healthcare. Today, clinical decision support systems are significant medical tools. The authors have developed a neural network system to diagnose liver failure. The "Neurodiagnost" system was tested in 270 patients with liver failure due to viral hepatitis B or C. As a result, clinical testing of the "Neurodiagnost" system demonstrated coincidence of neural network and laboratory diagnostics with a probability equal 91.5 % (247 patients). The use of the "Neurodiagnost" program can help reduce the risk of developing liver failure in surgery.

Persistent homology approach distinguishes potential pattern between “Early” and “Not Early” hepatic decompensation groups using MRI modalities

Abstract Primary sclerosis cholangitis (PSC) predisposes individuals to liver failure, but it is challenging for radiologists examining radiologic images to predict which patients with PSC will ultimately develop liver failure. Motivated by algebraic topology, a topological data analysis - inspired framework was adopted in the study of the imaging pattern between the “Early Decompensation” and “Not Early” groups. The results demonstrate that the proposed methodology discriminates “Early Decompensation” and “Not Early” groups. Our study is the first attempt to provide a topological representation-based method into early hepatic decompensation and not early groups.

Lumacaftor-ivacaftor effects on cystic fibrosis-related liver involvement in adolescents with homozygous F508 del-CFTR

BackgroundThe effects of lumacaftor-ivacaftor on cystic fibrosis transmembrane conductance regulator (CFTR)-associated liver disease remain unclear. The objective of the study was to describe the effect of this treatment on features of liver involvement in a cystic fibrosis (CF) adolescent population homozygous for F508del. MethodsClinical characteristics, liver blood tests, abdominal ultrasonography (US), and pancreas and liver proton density fat fraction (PDFF) by magnetic resonance imaging, were obtained at treatment initiation and at 12 months for all patients. Biomarkers of CFTR activity (sweat chloride test, nasal potential difference, and intestinal current measurement) were assessed at initiation and at 6 months therapy. ResultsOf the 37 patients who started ivacaftor/lumacaftor treatment, 28 were eligible for analysis. In this group, before treatment initiation, 4 patients were diagnosed with multinodular liver and portal hypertension, 19 with other forms of CF liver involvement, and 5 with no signs of liver involvement. During treatment, no hepatic adverse reactions were documented, and no patient developed liver failure. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyl transferase (GGT) decreased significantly following initiation of lumacaftor-ivacaftor, and remained so after 12 months treatment. This was not correlated with changes in clinical status, liver and pancreas US and PDFF, fecal elastase, or lumacaftor-ivacaftor serum levels. The most “responsive” patients demonstrated a significant increase in biomarkers of CFTR activity. ConclusionsThese results may suggest a potential beneficial effect of CFTR modulators on CF liver disease and warrant further investigation in larger, prospective studies.

Treatment of liver failure post one anastomosis gastric bypass by revising to normal anatomy: A case report.

IntroductionObesity and the associated metabolic syndrome are global health problems. Significant weight loss after bariatric surgery can cause a substantial difference in those comorbidities in obese patients. In this case, we described a rare complication of a patient who developed acute liver failure after an uneventful one anastomosis gastric bypass treated conservatively and revision of the one anastomosis gastric bypass to normal anatomy.Case presentationWe present a 52-year-old female known to have hypothyroidism and morbid obesity with a BMI of 45. For that, she underwent uneventful one anastomosis gastric bypass. Later, she developed liver failure and hepatic encephalopathy, which was managed conservatively and revision surgery to normal anatomy.DiscussionBariatric surgery plays an integral role in treating obese patients for its associated impacts, like facilitating weight loss and related metabolic syndrome improvement. The effects of bariatric surgery on liver functioning are controversial. Some malabsorptive procedures are linked to postoperative hepatic complications. However, it is uncommon in a recent new technique in bariatric surgery. Liver transplant and revision of the bariatric surgery have been described as management. However, optimal nutrition support without a liver transplant along with revision surgery is possible in experienced hands.ConclusionEarly detection of liver impairment and early intervention by a revision to normal anatomy by an experienced surgeon is considered the safest and most effective procedure for such patients. However, late detection where liver failure occurs, liver transplantation is the only effective treatment for preventing fatal outcomes.

Design of Inhibitory Peptides of the Interaction between the E2 Protein of the Hepatitis C Virus and the CD81 and CD209 receptors

Infection through the Hepatitis C virus does not have a vaccine and treatment with pegylated interferon and ribavirin can fail; which is why it may cause chronic infection and, consequently, could develop liver failure or hepatocellular carcinoma. It has been described that virus-cell recognition occurs between the E2 viral envelope protein and diverse cell receptors, with this interaction being critical in viral infection. which is why the study sought to identify inhibitory peptides of the interaction between viral E2 protein and the CD81 and CD209 receptors. Methodology: Through the RCSB protein database, crystals from the CD81 and CD209 receptors were selected, CD81/E2-HCV, CD209/E2-HCV complexes were carried out by SWISS-MODEL to generate inhibitory peptides of protein interaction through the Rosetta web server, this interaction was validated through ClusPro and finally, determined the theoretical physicochemical and cytotoxic properties of these peptides. Results: two peptides were obtained, without predicted toxicity, with a theoretical capacity of blocking the protein interaction between the E2 protein of the virus and CD81 and CD209.

The feasibility and safety in using acetaminophen with fentanyl for pain control after liver resection with regards to liver function: A prospective single-center pilot study in Japan.

Acetaminophen has been widely used as an analgesic agent after various types of surgery. However, acetaminophen may sometimes induce severe liver dysfunction, which can occasionally lead to the need for liver transplantation. The aim of this study was to assess the feasibility and efficacy of administering acetaminophen to patients after liver resection (LR). The prospective study included 50 patients who underwent the following procedures: partial LR (n=21) andmore than one section LR (n=29). Pain control was provided with continuous intravenous fentanyl and acetaminophen every 6hours (within 2days). We analyzed the liver function and blood concentration of acetaminophen at 1 and 3days after LR using high performance liquid chromatography (HPLC), and investigated the results of partial and more than one section LR, and also examined the degree of liver fibrosis. The alanine transaminase level on postoperative days 1, 5, and 7 and total bilirubin on postoperative days 1 to 5 after LR in patients with more than one section LR was significantly higher than the levels in patients with partial resection. No patients developed liver failure. The blood concentration of acetaminophen by HPLC was significantly elevated in patients with resection of more than one section in comparison to the partial resection group. The safety of acetaminophen was evaluated in Japanese patients who underwent different types of LR with different degrees of liver fibrosis.

Successful treatment with alectinib after crizotinib-induced hepatitis in ALK-rearranged advanced lung cancer patient: a case report

BackgroundBesides the clinical benefit of crizotinib in ALK-rearranged metastatic non-small cell lung cancer (NSCLC), concerns about its hepatotoxicity have arisen. It is not clear whether this is a drug class side effect or if the use of other selective ALKs inhibitors is safe after this serious adverse event. While evidence from clinical trials is scarce, reports of treatment after crizotinib-induces hepatitis may add to clinical decision.Case presentationHerein, we report a case of acute hepatitis induced by crizotinib in a 32-years-old female diagnosed with metastatic NSCLC, harboring the ALK-rearrangement. After 60 days of crizotinib therapy, the patient presented with acute hepatitis, diagnosed after investigation of non-specific symptoms, such as nausea and fatigue. Serum aspartate aminotransferase and alanine aminotransferase levels had increased from baseline to 3010 IU/L and 9145 IU/L, respectively. Total bilirubin increased up to 7.91 mg/dL, but she did not develop liver failure. After crizotinib discontinuation, a gradual hepatic function recovery occurred. Unfortunately, during the period without specific oncology treatment, her disease showed an unequivocal progression. Therefore, she started on alectinib with great response, and no liver function alteration recurred.ConclusionsThis case suggests that alectinib, even belonging to the same drug class, could be used as an alternative agent when crizotinib is the etiology of liver damage, but more robust evidence has awaited.

Regional liver function analysis with gadoxetic acid-enhanced MRI and virtual hepatectomy: prediction of postoperative short-term outcomes for HCC.

To explore the role of quantitative regional liver function assessed by preoperative gadoxetic acid-enhanced MRI with computer-aided virtual hepatectomy to predict short-term outcomes after major hepatectomy for HCC. We retrospectively reviewed the records of 133 consecutive patients with HCC who underwent preoperative gadoxetic acid-enhanced MRI and indocyanine green (ICG) test. Forty-five patients received open major hepatectomy. Liver function reserve and the future liver remnant were evaluated by computer-aided virtual hepatectomy. Global liver functional parameters included the T1 relaxation time reduction rate (T1ratio) and functional liver volume (FV), whereas regional parameters included the rT1pos, rT1ratio, remnant FV (rFV), and remnant FV ratio (rFVratio) of the remnant liver. The functional parameters of the MRI and ICG were used to predict the short-term outcomes (liver failure and major complications) after major hepatectomy. The T1ratio and FV were correlated with the ICG test (rho = - 0.304 and - 0.449, p < 0.05). FV < 682.8 ml indicated preoperative ICG-R15 ≥ 14% with 0.765 value of the area under the curve (AUC). No patient who underwent major resection with good liver functional reserve (ICG < 14%) and enough future remnant volume (> 30% standard LV) developed liver failure. Low rT1ratio (< 66.5%) and high rT1pos (> 217.5 ms) may predict major complications (AUC = 0.831 and 0.756, respectively; p < 0.05). The rT1ratio was an independent risk factor for postoperative major complications (odds ratio [OR] = 0.845, 95% CI, 0.736-0.966; p < 0.05). Preoperative gadoxetic acid-enhanced MRI with computer-aided virtual hepatectomy may facilitate optimal assessment of regional liver functional reserve to predict short-term outcomes after major hepatectomy for HCC. • Preoperative gadoxetic acid-enhanced MRI with virtual hepatectomy and volumetric analysis can provide precise liver volume and regional functional assessment. • Quantitative regional liver function assessed by gadoxetic acid-enhanced MRI can predict the short-term outcomes after major hepatectomy in patients with HCC. • The regional liver function assessed by gadoxetic acid-enhanced MRI is an independent risk factor for postoperative major complications.

Long-term clinical outcome of HBeAg-negative chronic hepatitis B patients who discontinued nucleos(t)ide analogues.

Discontinuation of nucleos(t)ide analogues (NA) remains a debatable issue in HBeAg-negative chronic hepatitis B (CHB). This study aimed to address the outcome of HBeAg-negative CHB patients who discontinued NA therapy. This prospective study included 57 non-cirrhotic HBeAg-negative Caucasian CHB patients who discontinued NA therapy after median virological remission of 6years. All patients had regular blood tests. Virological relapse was defined as HBV DNA>2000IU/mL or >20000IU/mL and biochemical relapse as ALT>ULN (40IU/mL) or >2xULN. All patients with retreatment predefined criteria restarted entecavir or tenofovir. Of the 57 patients, 29 remained without retreatment after median follow-up of 65months (range: 36-87) following treatment discontinuation. At 3, 6, 12, 24, 36 and 48months, cumulative rates of retreatment were 16%, 20%, 32%, 35%, 46% and 50%, while the proportion of patients with HBV DNA<2000IU/mL and ALT<ULN were 73%, 60%, 52%, 52%, 47% and 37% respectively. All patients had virological and biochemical response after retreatment. No patient developed liver failure, hepatocellular carcinoma or death. Cumulative rates of HBsAg loss were 2%, 4%, 7%, 10% and 20% at 3, 6, 12, 24 and 36months. HBsAg levels<100IU/mL at the end of NA treatment could predict HBsAg loss (P=.001). Our study supports that NA therapy can be safely stopped in non-cirrhotic patients with HBeAg-negative CHB. Over a median follow-up of more than 5years, half of the patients remained without retreatment with a substantial proportion of them achieving functional cure.

Correction possibilities of drug-induced liver toxicity in the treatment of patients with blood system tumors

Background. In modern oncohematology achieved notable success due to the intensification and development of new chemotherapy regimens. However, the side effects of anticancer drugs, due to low selectivity of most of them, are a serious limitation to achieve their maximal therapeutic effect. Although doctors are aware of the possibility of hepatotoxic reactions to various drugs, in clinical practice, the diagnosis of drug-induced liver injury is formulated unreasonably rarely. This speculation is due to several factors: in some cases, the latent course of drug-induced liver injury, often inadequate interpretation of clinical symptoms and laboratory parameters, and sometimes insufficiently thorough collection of anamnesis. A particularly difficult problem for a doctor is the development of drug-induced hepatotoxicity in patients for whom the “causal” drug is prescribed for vital indications, in particular, polychemotherapy in cancer patients, complex antimicrobial therapy and antiviral therapy for febrile neutropenia or sepsis, etc. In these situations, on the one hand, treatment cancellation is impossible due to the risk of disease progression, on the other hand, its continuation is undesirable due to the risk of severe hepatitis. In addition, multicomponent therapy, which is a complex of potentially hepatotoxic substances, often does not allow specifying the substance that caused the pathological reaction. At the same time, it is obvious that the hepatocyte, the main cell of the hepatic parenchyma, remains the center of the organ pathology. The variety of biochemical processes occurring with ademetionine participation served as the basis for conducting clinical studies in order to correct drug-induced liver toxicity in the treatment of patients with blood system tumors.The objective of the study is to assess laboratory and clinical parameters of drug-induced liver injury (DILI), intrahepatic cholestasis in the study of homeostasis disorders in patients with hematological malignancies and chemotherapy-induced hepatotoxicity.Materials and methods. The study involved 45 patients with blood system tumors, who had chemotherapy-induced hepatocellular failure. To describe the population of DILI patients, we collected demographic data, clarified the underlying liver disease in each patient, and analyzed the diagnostic criteria for chronic liver disease due to DILI. Clinical signs and symptoms of cholestasis (jaundice, pruritus, weakness), as well as manifestations of a depressive state and asthenic syndrome – mood (mild, moderate and severe), normalization of sleep rhythm, memory improvement, general health were assessed. Changes in laboratory parameters of liver function were studied. In 20 patients with blood system tumors, the biochemical parameters associated with cell metabolism were analyzed – lipid peroxidation, nitric oxide (NOx ) level, impaired liver detoxification capacity by glutathione level and glutathione-S-transferase activity. The treatment regimens for drug-induced hepatotoxicity included the Heptral, which was prescribed until stable normalization of liver function.Results. All patients with developed liver failure showed metabolic disorders. The use of ademetionine has shown significant effect. The NO and superoxide dismutase in most patients decreased significantly and almost corresponded to the norm. Normalization of the glutathione system parameters was also observed. One of the mechanisms of Heptral protective effect is an increase in the glutathione synthesis. The improvement in laboratory parameters was accompanied by the disappearance of DILI and intrahepatic cholestasis symptoms. This is confirmed by significant statistical correlations between them and indicates the ademetionine efficacy to recovery of hepatocytes function. When using ademetionine, the most pronounced reduction among biochemical parameters was observed in alkaline phosphatase and γ-glutamyl transpeptidase, markers of cholestasis syndrome. In addition, serum bilirubin concentration and alanine and aspartic transaminases activity (albeit to a lesser extent) decreased significantly. Clinical and biochemical effects, as a rule, persisted for several months after completion of therapy. Decrease in biochemical parameters characterizing cholestasis and cytolysis (positive dynamics of alanine and aspartic transaminases, alkaline phosphatase, γ-glutamyl transpeptidase, bilirubin) was accompanied by an improvement and normalization of patients’ well-being. When assessing the depression and asthenic syndrome, it was noted that the duration of Heptral therapy is important.Conclusion. The results obtained were the basis for the development of supportive therapy programs to prevent and reduce liver toxicity during chemotherapy. Rational approaches to the liver metabolic disorders correction – a real way to increase the treatment efficacy and improve the quality of life of patients with blood system tumors.

The effect of preoperative chemotherapy on liver regeneration after portal vein embolization/ligation or liver resection in patients with colorectal liver metastasis: a systematic review protocol

IntroductionLiver resection (LR) in patients with liver metastasis from colorectal cancer remains the only curative treatment. Perioperative chemotherapy improves prognosis of these patients. However, there are concerns regarding the effect of preoperative chemotherapy on liver regeneration, which is a key event in avoiding liver failure after LR. The primary objective of this systematic review is to assess the effect of neoadjuvant chemotherapy on liver regeneration after (LR) or portal vein embolization (PVE) in patients with liver metastasis from colorectal cancer. The secondary objectives are to evaluate the impact of the type of chemotherapy, number of cycles, and time between end of treatment and procedure (LR or PVE) and to investigate whether there is an association between degree of hypertrophy and postoperative liver failure.MethodsThis meta-analysis will include studies reporting liver regeneration rates in patients submitted to LR or PVE. Pubmed, Scopus, Web of Science, Embase, and Cochrane databases will be searched. Only studies comparing neoadjuvant vs no chemotherapy, or comparing chemotherapy characteristics (bevacizumab administration, number of cycles, and time from finishing chemotherapy until intervention), will be included. We will select studies from 1990 to present. Two researchers will individually screen the identified records, according to a list of inclusion and exclusion criteria. Primary outcome will be future liver remnant regeneration rate. Bias of the studies will be evaluated with the ROBINS-I tool, and quality of evidence for all outcomes will be determined with the GRADE system. The data will be registered in a predesigned database. If selected studies are sufficiently homogeneous, we will perform a meta-analysis of reported results. In the event of a substantial heterogeneity, a qualitative systematic review will be performed.DiscussionThe results of this systematic review may help to better identify the patients affected by liver metastasis that could present low regeneration rates after neoadjuvant chemotherapy. These patients are at risk to develop liver failure after extended hepatectomies and therefore are not good candidates for such aggressive procedures.Systematic review registrationPROSPERO registration number: CRD42020178481 (July 5, 2020).

Portosystemic shunt for portal hypertension after Kasai operation in patients with biliary atresia.

Many biliary atresia (BA) patients will eventually develop liver failure even after a successful Kasai portoenterostomy. A common complication of long-term BA survivors with their native liver is problematic portal hypertension. The aim of this study was to defend the view that portosystemic shunts can delay or negate the need for transplantation in these children. A retrospective single center review of the efficacy of portosystemic shunts in BA patients after a successful Kasai portoenterostomy was conducted. From 1991 to 2017, 11 patients received portosystemic shunts. Median age of Kasai operation was 48 (36-61) days. Shunts were performed at the median age of 6.2 (4.1-6.8) years. Three of these eleven patients required subsequent liver transplantation. OS at 5 and 10years were 90.9% and 81.8%, respectively. TFS at 5 and 10years were 90.9% and 72.7%, respectively. Long-term complications included mild encephalopathy in 2 patients, hypersplenism in 3, and cholestasis in 1. Portosystemic shunt for the treatment of portal hypertension in carefully selected BA patients is an effective option in delaying or negating the need for liver transplantation.

Clinical Features of Patients With COVID-19 With Nonalcoholic Fatty Liver Disease.

Previous studies reported that coronavirus disease 2019 (COVID‐19) was likely to result in liver injury. However, few studies investigated liver injury in patients with COVID‐19 with chronic liver diseases. We described the clinical features in patients with COVID‐19 with nonalcoholic fatty liver disease (NAFLD). Confirmed patients with COVID‐19 from hospitals in 10 cities of Jiangsu Province, China, were retrospectively included between January 18, 2020, and February 26, 2020. The hepatic steatosis index (HSI) was used to defined NAFLD. A total of 280 patients with COVID‐19 were enrolled. Eighty‐six (30.7%) of 280 patients with COVID‐19 were diagnosed as NAFLD by HSI. One hundred (35.7%) patients presented abnormal liver function on admission. The median alanine aminotransferase (ALT) levels (34.5 U/L vs. 23.0 U/L; P < 0.001) and the proportion of elevated ALT (>40 U/L) (40.7% vs. 10.8%; P < 0.001) were significantly higher in patients with NAFLD than in patients without NAFLD on admission. The proportion of elevated ALT in patients with NAFLD was also significantly higher than patients without NAFLD (65.1% vs. 38.7%; P < 0.001) during hospitalization. Multivariate analysis showed that age over 50 years (odds ratio [OR], 2.077; 95% confidence interval [CI], 1.183, 3.648; P = 0.011) and concurrent NAFLD (OR, 2.956; 95% CI, 1.526, 5.726; P = 0.001) were independent risk factors of ALT elevation in patients with COVID‐19, while the atomized inhalation of interferon α‐2b (OR, 0.402; 95% CI, 0.236, 0.683; P = 0.001) was associated with a reduced risk of ALT elevation during hospitalization. No patient developed liver failure or death during hospitalization. The complications and clinical outcomes were comparable between patients with COVID‐19 with and without NAFLD. Conclusion: Patients with NAFLD are more likely to develop liver injury when infected by COVID‐19. However, no patient developed severe liver‐related complications during hospitalization.

A case series of COVID-19 patients with chronic hepatitis B virus infection.

Previous studies reported that coronavirus disease 2019 (COVID‐19) was likely to result in liver injury. However, few studies reported the impacts of COVID‐19 on liver function in patients with chronic liver diseases. We aimed to describe a case series of COVID‐19 patients with chronic hepatitis B virus (HBV) infection. Confirmed hospitalized COVID‐19 patients from hospitals in 10 cities of Jiangsu province, China, were retrospectively included between 18 January 2020 and 26 February 2020. Demographic information, epidemiologic data, clinical features, and treatment data were extracted from medical records. Seven COVID‐19 patients with chronic HBV infection were included. Six (85.7%) patients were male. The patients aged from 33 to 49 years. Two patients had HBV‐related cirrhosis. One patient (14.3%) was positive for serum HBV e‐antigen. On admission, 1 (14.3%) patient had mildly elevated alanine aminotransferase (ALT) level (>40 U/L) and 1 (14.3%) had elevated aspartate aminotransferase (AST) level (>40 U/L). The serum albumin level and platelet counts were decreased in two patients with HBV‐related liver cirrhosis. Three (42.9%) patients had elevated ALT level and 2 (28.6%) patients had elevated AST level in hospitalization. However, the peak ALT and AST level during hospitalization was 51 U/L and 44 U/L, respectively. As of 29 February 2020, all patients were discharged. No patient was admitted to the intensive care units or developed liver failure during hospitalization. The abnormalities of liver function are not uncommon on COVID‐19 patients with chronic HBV infection in our case series. However, no patient developed severe liver‐related complications during hospitalization.

Living donor liver transplantation for more than 30-year survived patients with native liver after Kasai operation for biliary atresia

ObjectivesA number of patients have developed liver failure after the Kasai operation for biliary atresia (BA), even after long-term postoperative course. We report our experience regarding four cases of biliary atresia required and treated with living donor liver transplantation (LDLT) during adulthood. MethodsAll four patients underwent Kasai operation for BA from 1974 to 1983 and had been followed-up for more than 30 years in our institute. Then, they developed liver failure and treated with LDLT. These four patients’ records were reviewed retrospectively. All data are described using the median value. ResultsThree female and one male were included. Kasai operation was performed at the age of 61 days. The type of biliary obstruction was type III-b1-ν in all. The survival period of the native liver was 440 months. The age at LDLT was 37 years. The reasons of deterioration of native liver were recurrent cholangitis in two and pregnancy and delivery in other two. The age of living donor was 40 years. Right liver grafts were used in all. Percentage of the real graft volume per standard liver volume was 47%. All patients were alive and overall graft survival rate was 100% at a follow-up period of 65 months after LDLT. ConclusionEven after more than 30 year-survival with native liver after Kasai operation, liver failure may be caused by recurrent cholangitis or pregnancy and delivery. LDLT may be effective treatment for those adult patients if an adequate living donor is available.

Imbalance Between α1‐Antitrypsin and Neutrophil Elastase in Simple Steatosis Promotes Inflammation and Fibrosis Through Regulation of Adenosine a3 Receptor Signaling in Non‐alcoholic Steatohepatitis

Study objectivesNon‐alcoholic fatty liver disease (NAFLD) has been considered leading cause of developing liver failure. However, the underlying mechanisms for transition from benign steatosis to clinically significant non‐alcoholic steatohepatitis (NASH) and non‐alcoholic steatofibrosis (NASF) have not been fully understood.MethodIn mouse model, NAFLD was induced by fast food diet (FFD) with a high glucose‐fructose solution for 24 weeks. For secretome proteomics, we used primary hepatocytes (HPs) isolated from normal chow diet (NCD) or FFD‐fed liver. The biased agonist of A3 adenosine receptor (A3AR), FM101 was utilized for the study of A3AR signaling.ResultsIn secretome proteomics, we found α1‐antitrypsin (A1AT) was decreased 0.2‐fold in FFD hepatocytes compared with NCD hepatocytes. Consistently, serum levels of A1AT from mice and human patients with NAFLD were significantly decreased compared to normal group. Conversely, the mRNA and protein level of Neutrophil Elastase (NE) were increased in FFD‐fed liver compared to NCD‐fed liver. We next confirmed inflammatory role of NE in Kupffer cells (KCs) as various cytokines (CCL2, TNF‐α, IL‐1β, iNOS and IL‐6) were increased in KCs with treatment of NE. Of note, NE has been reported to exert proteolytic activity that can prevent activation of G‐protein‐coupled receptors (GPCRs). We observed similar proteolysis that A3AR, a member of the adenosine receptor group of GPCRs, was cleaved in hepatic stellate cells (HSCs) after treatment of NE, indicating that A1AT‐NE system may regulate the A3AR signaling. Interestingly, A3AR was predominantly expressed in KCs and HSCs, but not in HPs. In vitro activation of A3AR signaling with FM101 significantly inhibited activation of KCs and HSCs as demonstrated by inflammatory cytokines (TNF‐α, IL‐6 and IL‐1β), and profibrogenic genes (Col1a1, Timp1 Acta2) expression, respectively. Moreover, in vivo activation of A3AR with FM101, lowered liver weight, liver to body ratio, and serum level of ALT and cholesterol induced by FFD. Furthermore, FM101 effectively improved steatofibrosis as assessed by quantification of collagen deposition. Mechanistically, FM101 treatment strongly blocked mitochondrial oxidative phosphorylation. Using pMito‐Timer and Mt‐Keima system, we observed FM101‐induced mitochondria vulnerability as demonstrated by increased accumulation of damaged mitochondria and subsequence mitophagic degradation. Consequently, CCCP‐induced cell death in macrophage was further enhanced by FM101 treatment.ConclusionsThe imbalance between A1AT and NE in simple steatosis mediates the progression of NASH and NASF through proteolytic inactivation of A3AR in KCs and HSCs. Thus, A3AR agonism with FM101 may have therapeutic potentials for treatment of NAFLD.Support or Funding InformationNational Research Foundation of Korea (NRF) ‐ 2019R1A2C1090178FM101 ameliorates FFD‐induced steatohepatitis and stetofibrosisFigure 1Adenosine A3 receptor signaling contributes to mitochondria vulnerabilityFigure 2

Radiological Presentation of a Patient With Multiple Sclerosis and Hepatic Disorder

In this case study, we presented the radiological characteristics of a 43-year-old female patient diagnosed with Multiple Sclerosis (MS). Following mitoxantrone administration, she developed liver failure. Magnetic Resonance Imaging (MRI) revealed multiple periventricular lesions in T2 and bilateral involvement of putamen and Globus Pallidus (GP) areas in T1 sequences.

Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV co-infection

The outcome of HBV infection, including the dynamics of HBsAg and HBV virological reactivation, among patients coinfected with HCV receiving direct-acting antivirals (DAAs) remains unclear. Thus, we aimed to analyze HBV-related outcomes in these patients. Serial HBsAg and HBV DNA levels were measured in 79 HBV/HCV-coinfected patients receiving DAAs (13 receiving anti-HBV nucleot(s)ide analog [NUC] therapy simultaneously). The endpoints included HBsAg dynamics and seroclearance, HBV reactivation (HBV DNA >1 log increase or >100 IU/ml if undetectable at baseline) and HBV-related clinical reactivation. HBsAg levels declined from a median of 73.3 IU/ml at baseline to 16.2 IU/ml at the end-of-DAA treatment and increased to 94.1 IU/ml at 12 months post-treatment. During a mean 11.1-months of follow-up, 8 (10.1%) patients experienced HBsAg seroclearance and 30 (38.0%) HBV reactivation (12-month cumulative incidence, 10.3% and 40.4%, respectively). Patients with pre-treatment HBsAg ≤10 IU/ml had a significantly higher rate of HBsAg seroclearance (hazard ratio [HR] 8.52; 95% CI 1.048-69.312) and lower risk of HBV reactivation than those with pre-treatment HBsAg >10 IU/ml (HR 2.88; 95% CI 1.057-7.844) in multivariate analyses. Six patients (4 cirrhotics) not receiving NUC therapy experienced HBV-related clinical reactivation; 3 of the 4 cirrhotics developed liver failure and 2 died despite immediate NUC therapy. Compared to untreated HBV-monoinfected patients, HBV/HCV-coinfected patients without NUC prophylaxis had a similar rate of HBsAg seroclearance, but a significantly higher risk of HBV reactivation following DAA therapy (HR 6.59; 95% CI 2.488-17.432). DAA-treated HBV/HCV-coinfected patients had significantly higher rates of HBV seroclearance, particularly among those with low pre-treatment HBsAg titer, but were at higher risk of HBV reactivation, particularly among those with higher pre-treatment HBsAg titer. Prophylactic anti-HBV therapy is essential for cirrhotic patients, irrespective of baseline HBV DNA levels. We studied outcomes relating to hepatitis B virus (HBV) in patients coinfected with both hepatitis B and C. Patients receiving direct-acting antiviral treatment for hepatitis C were more likely to experience seroclearance (or functional cure of HBV), but were also more likely to experience HBV reactivation, which can lead to hepatitis, liver failure and death. In coinfected cirrhotic patients being treated for HCV, prophylactic treatment for HBV is mandatory.

Intoxicación por fósforo blanco durante fiestas decembrinas: a propósito de un caso

White is the most common form of the available phosphorus. It is highly reactive and is present in different chemical products. In Colombia, it is used for the preparation of pyrotechnic products. When accidental or voluntary intake occurs, the main risks are hepatic and renal, in addition to injuries from skin burns and hemodynamic compromise. The article describes a case report of a 10-month-old patient who inadvertently ingested pyrotechnic powder, but failed to develop liver failure. N-Acetylcysteine (NAC) was used to increase Glutathione synthesis and prevent clinical progression.

Selective occlusion of the hepatic artery and portal vein improves liver hypertrophy for staged hepatectomy

BackgroundTo evaluate the safety and feasibility of selective occlusion of the hepatic artery and portal vein (SOAP) for staged hepatectomy (SOAPS) in patients with hepatocellular carcinoma (HCC)MethodsFrom December 2014 to August 2018, 9 patients with unresectable HCC were chosen to undergo SOAPS. SOAP without liver partition was performed in the first stage. The second stage was performed when future liver remnant (FLR) was equal to or bigger than 40% of the standard liver volume (SLV). The growth rate of FLR, perioperative outcomes, and survival data was recorded.ResultsIn the first stage, all the 9 patients completed SOAP. Two cases received radiological interventional method and 7 cases received open operation. None of them developed liver failure and died following SOAP. After SOAP, FLR increased 145.0 ml (115.0 to 210 ml) and 37.1% (25.6 to 51.7%) on average. The average time interval between the two stages was 14.1 days (8 to 18 days). In the second stage, no in-hospital deaths occurred after SOAPS. One patient suffered from liver failure after SOAPS, and artificial liver support was adopted and his total bilirubin level returned to normal after postoperative day 35. The alpha-fetoprotein level of 8 patients reduced to normal within 2 months after SOAPS. Among 9 patients, 5 patients survived, 4 patients died of intrahepatic recurrence, lung metastasis, or bone metastasis. In the 5 survived cases, bone metastasis and intrahepatic recurrence were found in 1 patient, intrahepatic recurrence was found in another patient, and the remaining 3 patients were free of recurrence. The median disease-free survival time and overall survival time were 10.4 and 13.9 months, respectively.ConclusionSOAP can facilitate rapid and sustained FLR hypertrophy, and SOAPS is safe and effective in patients with unresectable HCC.