Hepatology Forum最新文献

Background and aim: Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver failure with poor outcomes. The present study aimed to evaluate the predictive values of D-dimer in patients with HE.

Materials and methods: Patients with chronic liver failure (CLF) and HE were enrolled. Univariate and multivariate logistic analysis was performed to investigate the risk factors for 1-year mortality of HE.

Results: During the first year after diagnosis, 39.2% (65/166) of the patients died. D-dimer was significantly higher in non-survivors (Z=2.617, p<0.01). Both D-dimer and international normalized ratio (INR) positively correlated with Child-Pugh and MELD scores, and negatively correlated with sodium (all p<0.01). Moreover, there was a negative relationship between D-dimer and HE grades (r=-0.168, p=0.031), while the relationship between INR and HE grades was not significant (r=0.083, p=0.289). Multivariate analysis showed that age (odds ratio (OR):1.035, 95% CI:1.004-1.067, p=0.03), D-dimer (OR=1.138, 95% CI:1.030-1.258, p=0.01), ALT (OR=1.012, 95% CI:1.001-1.022, p=0.03), and sodium (OR=0.920, 95% CI:0.858-0.986, p=0.02) were independent risk factors for 1-year mortality. Then, a new model Model(Age_DD_ALT_Na) incorporating age, D-dimer, ALT, and sodium was developed. AUROC of Model(Age_DD_ALT_Na) was 0.732, which was significantly higher than MELD and Child-Pugh scores (AUROC: 0.602 and 0.599, p=0.013 and 0.022).

Conclusion: D-dimer is a prognostic marker for 1-year mortality in patients with CLF and HE.

Hepatopulmonary syndrome (HPS) is a pulmonary complication of liver cirrhosis that causes an oxygenation defect. Many patients are asymptomatic at diagnosis or may have non-specific symptoms such as dyspnea. Since the diagnostic criteria for HPS have been established, its prevalence has been better estimated. HPS is an important prognostic indicator for patients undergoing evaluation for liver transplant. The implementation of the Model for End-stage Liver Disease exception policy has improved the outcomes of HPS; however, the mortality remains high. Here, we discuss the pathophysiology, diagnostic criteria, and recent experimental studies in HPS.

Substance use disorders are a global health problem with detrimental effects on one's health, wealth, and stealth. It includes the use of prescribed medications or the use of illicit drugs in excess amounts or for excess durations associated with complex neuropsychiatric and/or physical manifestations. It affects every organ in the body, and the liver is no exception to the deleterious effects of substance abuse. The mechanism of liver injury varies from agent to agent and may include direct toxic effects, oxidative stress, and inflammatory responses. The hepatic involvement ranges from asymptomatic liver enzyme elevation and fatty liver disease to hepatitis, liver failure, and cirrhosis. Alcohol, the most frequent agent implicated in substance use disorder, is also a prototype hepatotoxin, capable of inducing the whole spectrum of liver diseases. Cigarette smoke contains numerous harmful chemicals, including carcinogens, which can induce liver injury, fibrosis, and HCC. Cocaine, particularly in acute overdose, can result in ischemic hepato-necrosis, while it can also result in clinically inapparent transaminasemia. Marijuana and opiates, despite being associated with numerous deleterious effects, are rarely implicated in clinically apparent liver injury. Individuals with substance use disorder are also prone to viral hepatitis and hepatic insults secondary to hypotension, hypoxia, and other systemic ailments. Liver transplant candidacy in individuals with substance use disorder is a highly complex arena, with guidelines balancing abstinence requirements against evolving evidence on outcomes. This review article provides a thorough analysis of the hepatotoxic repercussions stemming from the agents commonly implicated in substance abuse disorders.

Background and aim: Hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis with evolving diagnostic criteria. This study aimed to examine HRS prevalence, subtypes, and outcomes while comparing previous and current diagnostic criteria.

Materials and methods: This is a retrospective observational clinical study conducted on hospitalized patients with decompensated cirrhosis. Demographic characteristics, comorbidities, disease duration, disease severity, length of hospitalization, number of rehospitalizations, cirrhosis etiologies, laboratory data, and clinical outcomes were reviewed. The criteria from 2007 by the International Club of Ascites were the previous ones, with the 2015 criteria being the current criteria for diagnosing HRS. The incidence of HRS and its subtypes was determined, and the clinical characteristics of patients with and without HRS were compared using the Mann-Whitney U test.

Results: The study enrolled 212 patients, with a male predominance (57.5%) and a mean age of 63.4±14.5 years. A total of 32.1% of patients developed acute kidney injury (AKI), with prerenal azotemia being the most common type (76.5%), followed by intrinsic renal AKI (23.5%). Under the current criteria, 27 patients (12.7%) received an HRS diagnosis, while under the previous criteria, 16 patients (7.5%) received an HRS diagnosis, and the difference in diagnostic frequencies was statistically significant (p=0.046). In HRS cases, the MELD score (p=0.001), being classified as Child-Pugh C (p=0.043), rehospitalization (p=0.011), requiring intensive care (p=0.001), and creatinine levels (p<0.001) were higher.

Conclusion: AKI is common in hospitalized cirrhotic patients. The current HRS criteria identify more cases that need close monitoring compared to the previous criteria.

Drug dose efficacy/toxicity depends on a number of factors including genetic and nongenetic factors, a pre-existing disease, and coadministration of other substances and drugs. Cytochrome P450 (CYP) proteins play a crucial role in drug metabolism where they catalyse a number of Phase I oxidation reactions. Concurrently administered drugs and substances, besides the CYP genotype are crucial and can induce/inhibit the CYP activity, thus affecting drug biotransformation and its bioavailability, compromising with drug efficacy, or even causing toxicity due to slow metabolism. Hepatic CYP is particularly important as it metabolizes about ¾ of all drugs. Determining the metabolite/drug ratio (in vivo CYP phenotyping) can be an important tool that can help in drug dose optimization for the drugs metabolized by specific CYPs as the genotype may not always reflect the true enzyme activity. Clinically important CYP isoforms commonly reported in drug oxidation reactions and which mainly include CYP3A4/5, CYP2C19, CYP2C9 and CYP2D6 need to be analysed for their activity in vivo, in at least the cases of unpredictable treatment outcomes. The activity levels of other less commonly reported but no less important CYPs, such as CYP2B6, one of the most polymorphic human CYP involved in the metabolism of artemisinin, bupropion, cyclophosphamide, efavirenz, ketamine and methadone, and reported for its high inter-individuals and within-individual variability may also be determined on a case-to-case basis. This review highlights the variations in CYP activity due to various reasons and the importance of in vivo phenotyping over genotype in ascertaining drug bioavailability and dose optimization, implicating metabolite/drug ratio determination for personalized treatment of especially chronic liver disease patients.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, potentially life-threatening, drug-induced hypersensitivity reaction that involves hematological abnormalities (atypical lymphocytosis, eosinophilia), lymphadenopathy, skin eruption, and internal organ involvement (lung, liver, kidney). The 36-year-old female patient was followed by bloody diarrhea, diffuse skin rashes and hepatitis. She was diagnosed with psoriatic arthritis, and Leflunomide 20 mg was added to the treatment six weeks ago. Upon developing hepatic encephalopathy and deepening the fulminant liver failure during the follow-up, a living donor liver from her son was transplanted on the 4^th day of hospitalization. The patient had deceased on the second day after liver transplantation due to multiple organ failures. In the literature, mortality in DRESS syndrome is mostly secondary to hepatic failure. Liver transplantation cannot be effective due to systemic involvement and recurrence in the transplanted liver.

Background and aim: The aim of this study was to evaluate the role of intrabiliary pressure (IBP) in the pathophysiology of extrahepatic biliary obstruction (EHBO) during percutaneous transhepatic biliary drainage (PTBD).

Materials and methods: Adult patients with EHBO who underwent PTBD were prospectively enrolled. IBP was recorded during primary PTBD. The parameters of interest were age, gender, etiology of EHBO, baseline and post-PTBD liver function tests, duration for resolution of jaundice (decrease in total serum bilirubin ≥30% of baseline or <2 mg/dL), cholangitis, bile cultures, and serum albumin levels. The level of EHBO was divided into three types: Type 1 - secondary biliary confluence involved; Type 2 - primary biliary confluence involved; Type 3 - mid and distal common bile duct obstruction.

Results: IBP was measured in 102 patients, and finally, 87 patients, including 52 (59.77%) females, were analyzed. The mean age of the patients was 56.1±11.6 years. The most common etiology of EHBO was carcinoma of the gallbladder in 44 (50.6%) patients. The mean IBP was 18.41±3.91 mmHg. IBP was significantly higher in Type 3 EHBO compared to Type 1 and 2 (p=0.012). A significant correlation was seen between IBP and baseline total serum bilirubin (p<0.01). There was a negative correlation between IBP and baseline serum albumin (p=0.017). In 56.3% of patients, resolution of jaundice was observed by day 3, but this was not significantly associated with IBP (p=0.19). There was no correlation between IBP and cholangitis (p=0.97) or bacterial cultures (p=0.21).

Conclusion: IBP was significantly associated with the type of EHBO, baseline serum bilirubin, and albumin levels. IBP could not predict cholangitis or the resolution of jaundice after PTBD.

Background and aim: Cirrhosis is characterized by structural and functional alterations of the liver. Melatonin (MLT) has antioxidant properties. Physical exercise (EX) can reverse muscle loss in cirrhotic patients. The objective was to evaluate the action of MLT and EX on the liver of rats subjected to the experimental model of bile duct ligation (BLD).

Materials and methods: 48 male Wistar rats were used, divided into groups: Control (CO), CO+MLT, CO+EX, CO+MLT+EX, BDL, BDL+MLT, BDL+EX, and BDL+MLT+EX. The treatments occurred from the 15^th to the 28^th day. The dose of MLT was 20 mg/kg via I.p (1x/day), and the EX was performed 10 min/day. Blood and liver were collected for analysis.

Results: The liver integrity enzymes AST, ALT, and ALP showed a significant reduction in the groups treated with MLT and EX. Histological analyses showed reorganization of the liver parenchyma, reduction of inflammatory infiltrate, and fibrotic nodules. Lipoperoxidation (LPO), the activity of antioxidant enzymes, and nitric oxide metabolites showed a significant reduction in the groups treated with MLT and EX. The expression of TNF-α and NF-kB decreased in the treated groups.

Conclusion: Melatonin and physical exercise seem to be effective in restoring the parameters evaluated in this model of experimental cirrhosis.

Background and aim: The triglyceride glucose index (TyG) has been proposed as a promising indicator of both insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). However, the efficacy of the TyG index in predicting NAFLD has not been adequately studied, particularly in obese individuals.

Materials and methods: We analyzed 190 morbidly obese individuals. The TyG index, anthropometric obesity indices, homeostatic model assessment (HOMA-IR), and biochemical parameters were compared. NAFLD was diagnosed by hepatic ultrasonography and classified into four grades (0, 1, 2, and 3). Individuals in grades 2 and 3 are considered to have severe steatosis, while those in grades 0 and 1 do not.

Results: The area under the curve (AUC) values of the TyG index, body mass index, neck circumferences, waist-to-hip ratio, and HOMA-IR did not differ significantly in predicting severe steatosis (0.640, 0.742, 0.725, 0.620, and 0.624 respectively). However, the AUC values of waist circumference and alanine aminotransferase provided better predictions than the TyG index (0.782, 0.744, and 0.640 respectively).

Conclusion: The TyG index is highly effective in predicting both the presence and severity of NAFLD. However, it did not outperform simple obesity indices in predicting NAFLD and its severity in obese patients.