Livers, Volume 2, Issue 3 (September 2022) – 12 articles

Polyamines (PAs), endogenous metabolites with a wide range of biological activities, are synthesized at a high rate in liver supporting hepatocyte proliferation and survival. The liver appears as an important regulator of plasma PAs; however, the perspective to exploit plasma PA measurements as indicators for liver function was not explored. This study aimed to evaluate the value of the plasma levels of PAs as a biomarker of pathological changes in the liver in patients with obstructive cholecystitis. The levels of polyamines and their acetylated forms were measured using HPLC/UV in the plasma of patients with obstructive cholecystitis and in healthy subjects. PA turnover was assessed by the ratio between an acetylated form of PA and PA. An effect of diet preference of cheese or meat, the major exogenous sources of PAs, smoking, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in anamnesis was also evaluated in healthy subjects. We found that the plasma levels of spermine and acetylated spermidine decreased in patients with obstructive cholecystitis without a concurring increase in the total plasma bilirubin and amylase levels. The turnover of spermine and spermidine was also changed, suggesting a decrease in the rate of PA degradation in the liver. In healthy subjects, the PA levels tended to mirror chronic smoking and recent SARS-CoV-2 infection but were not relevant to diet factors. A number of observations indicated the role of physical exercise in the regulation of the plasma pool of PA. The decrease in plasma PA levels and index of PA turnover in the cholestasis syndrome indicate the liver’s metabolic function reduction. A conceivable effect of lung-related conditions on plasma PA, while indicating low specificity, nonetheless, speaks favorably about the high sensitivity of plasma PA measurement as an early diagnostic test in the clinic. Full article

Background: Spontaneous bacterial peritonitis (SBP) is defined as a bacterial infection of the ascitic fluid without a surgically treatable intra-abdominal infection source. SBP is a common, severe complication in cirrhosis patients with ascites, and if left untreated, in-hospital mortality may exceed 90%. However, the incidence of SBP has been lowered to approx. 20% through early diagnosis and antibiotic therapy. Clinical awareness, prompt diagnosis, and immediate treatment are advised when caring for these patients to reduce mortality and morbidity. Aim: To discuss important issues comprising types of SBP, pathogenesis, bacteriology, including the emergence of multidrug-resistant (MDR) microorganisms, prompt diagnosis, risk factors, prognosis, treatment strategies, as well as recurrence prevention through antibiotic prophylaxis until liver transplantation and future trends in treating and preventing SBP in detail. Methods: This article is a literature review and appraisal of guidelines, randomized controlled trials, meta-analyses, and other review articles found on PubMed from between 1977 and 2022. Results: There are three types of SBP. Bacterial translocation from GI tract is the most common source of SBP. Therefore, two thirds of SBP cases were caused by Gram-negative bacilli, of which Escherichia coli is the most frequently isolated pathogen. However, a trend of Gram-positive cocci associated SBP has been demonstrated in recent years, possibly related to more invasive procedures and long-term quinolone prophylaxis. A diagnostic paracentesis should be performed in all patients with cirrhosis and ascites who require emergency room care or hospitalization, who demonstrate or report consistent signs/symptoms in order to confirm evidence of SBP. Distinguishing SBP from secondary bacterial peritonitis is essential because the conditions require different therapeutic strategies. The standard treatment for SBP is prompt broad-spectrum antibiotic administration and should be tailored according to community-acquired SBP, healthcare-associated or nosocomial SBP infections and local resistance profile. Albumin supplementation, especially in patients with renal impairment, is also beneficial. Selective intestinal decontamination is associated with a reduced risk of bacterial infection and mortality in high-risk group. Conclusions: The standard treatment for SBP is prompt broad-spectrum antibiotic administration and should be tailored according to community-acquired SBP, healthcare-associated or nosocomial SBP infections and local resistance profile. Since the one-year overall mortality rates for SBP range from 53.9 to 78%, liver transplantation should be seriously considered for SBP survivors who are good candidates for transplantation. Further development of non-antibiotic strategies based on pathogenic mechanisms are also urgently needed. Full article

Liver cancer ranks as the fourth leading cause of cancer-related deaths. Despite extensive research efforts aiming to evaluate the biological mechanisms underlying hepatocellular carcinoma (HCC) development, little has been translated towards new diagnostic and treatment options for HCC patients. Historically, the focus has been centered on coding RNAs and their respective proteins. However, significant advances in sequencing and RNA detection technologies have shifted the research focus towards non-coding RNAs (ncRNA), as well as their impact on HCC development and progression. A number of studies reported complex post-transcriptional interactions between various ncRNA and coding RNA molecules. These interactions offer insights into the role of ncRNAs in both the known pathways leading to oncogenesis, such as dysregulation of p53, and lesser-known mechanisms, such as small nucleolar RNA methylation. Studies investigating these mechanisms have identified prevalent ncRNA changes in microRNAs, snoRNAs, and long non-coding RNAs that can both pre- and post-translationally regulate key factors in HCC progression. In this review, we present relevant publications describing ncRNAs to summarize the impact of different ncRNA species on liver cancer development and progression and to evaluate recent attempts at clinical translation. Full article

Gallbladder percutaneous tissue sampling is a not-so-common technique in cytohistological diagnosis of gallbladder tissue or masses, which can be useful in cases of surgically unresectable disease and unfeasible endoscopic assessment to address the most adequate chemotherapy course. Nonetheless, gallbladder percutaneous tissue sampling can be of great utility in the patient’s diagnostic and therapeutic work-up. This article summarizes the literature evidence on gallbladder biopsy techniques, complications, and technical precautions for a safe and effective sampling. Full article

In liver research, immortalized cell lines have assumed an important role in studying general physiological and pathological processes. However, misidentification and cross-contamination of cell lines is a widespread problem in biomedical sciences resulting in irreproducible results and false conclusions. Although the huge impact of working with wrong cell lines on life science research and publication has been well recognized, there are only limited efforts and strategies to prevent cell misidentification. This commentary provides a catalogue of the most important cell lines used in hepatology research, examples of misidentified cell lines, and short guidelines to be considered when working with continuous lines. Full article

Malnutrition in cirrhotic patients is extremely common and has a multifactorial aetiology, whose constitutive elements have not been completely elucidated yet. Protein depletion is particularly important and an imbalance of hormones regulating hunger and satiety may be an important additive factor. The diagnosis and treatment of malnutrition are extremely important since malnutrition is associated with higher complication rates and mortality. Our observational study aimed to study protein status and energy intake-related hormone levels in a cohort of hospitalized cirrhotic patients. We enrolled 50 hospitalized and clinically stable cirrhotic patients and assessed their nutritional status with anthropometric measurements and nitrogen balance. In a subgroup of 16 patients and 10 healthy controls, circulating ghrelin and leptin levels were studied. We observed that 60% of our patients were malnourished on the basis of the mid-arm muscle circumference values; the recorded daily protein intake was tendentially insufficient (mean protein intake of 0.7 ± 0.5 g protein/kg vs. recommended intake of 1.2–1.5 g of protein/kg/die). Cirrhotic patients had lower circulating levels of both ghrelin and leptin compared to healthy controls. In conclusion, hospitalized cirrhotic patients face a catabolic state and an imbalance in hormones regulating food intake and satiety, and these elements may play a major role in the genesis and/or the worsening of malnutrition. Full article

Nonalcoholic fatty liver disease (NAFLD) is the main cause of liver disease. The physiopathological processes involved in the disease are metabolic syndrome (MetS) components (central obesity, dyslipidemia, insulin resistance/type 2 diabetes, hypertension), genetic, and dietary factors, including unsaturated fats and sweetened beverages, which are able to lead to inflammation and oxidative stress, conditions associated with progression and severity of NAFLD. Gamma-oryzanol (γOz) is a nutraceutical obtained from rice brain oil with many benefits to health, from immunological to metabolic. The aim of this study is to test the preventive effect of γOz on the physiopathological process related to nonalcoholic fatty liver disease in animals submitted to high sugar/fat diet. Male Wistar rats (±187 g) were randomly divided into four experimental groups to receive: control diet (C, n = 6), control diet plus γOz (C + γOz, n = 6), high sugar/fat diet (HSF, n = 6), or high sugar/fat diet plus γOz (HSF + γOz, n = 6) during 30 weeks. HSF groups also received water plus sucrose (25%). γOz was added to diets to reach 0.5% of final concentration. The HSF group presented MetS, liver inflammation and oxidative stress, and micro and macrovesicular steatosis. HSF plus γOz was protected against these changes. It is possible to conclude that gamma-oryzanol was effective in modulating the physiopathological process related to nonalcoholic fatty liver disease in animals submitted to a high sugar/fat diet. Full article

Microbiome-derived short chain fatty acids (SCFAs: acetate, propionate, and butyrate) and bile acids (BAs: primary BAs and secondary BAs) widely influence liver metabolic inflammation, immune responses, and carcinogenesis. In recent literature, the role of SCFAs and BAs in various liver diseases has been discussed. SCFAs and BAs are two types of microbiome-derived metabolites and they have been shown to have immunoregulatory ability in autoimmunity, inflammation, and liver-cancer microcellular environments. SCFAs and BAs are dependent on dietary components. The numerous regulatory processes in lymphocytes and non-immune cells that underpin both the positive and harmful effects of microbial metabolites include variations in metabolic signaling and epigenetic states. As a result, histone deacetylase (HDAC) inhibitors, SCFAs, and BAs, which are powerful immunometabolism modulators, have been explored. BAs have also been shown to alter the microbiome as well as adaptive and innate immune systems. We therefore emphasize the important metabolites in liver disease for clinical therapeutic applications. A deep understanding of SCFAs and Bas, as well as their molecular risk, could reveal more about certain liver-disease conditions. Full article

Herbal and dietary supplement (HDS) use has grown exponentially in the United States. Unfortunately, the incidence of HDS-related liver injury has proportionally increased. Despite the potential for certain HDSs to cause clinically significant liver injury, they are not regulated by the Food and Drug Administration. Recent efforts have been made to regulate HDSs but are far removed from the scrutiny of prescription medications. Scant literature exists on HDSs and their risks of causing liver injury. In this comprehensive review, we examine trends of HDS use in the United States and the pathophysiologic mechanisms of drug-induced liver injury (DILI) of certain HDSs. Finally, we review usage rates; benefits, if any; purported pathophysiology of DILI; and propensity for progression to fulminant hepatic failure of nine HDSs linked to clinically significant DILI. Full article

Knowledge regarding the prevalence of the hepatitis E virus (HEV) in the general population can indicate public health and personal hygiene practices in a community. HEV spreads through the fecal-oral route and contaminates drinking water through sewage. Moreover, poverty also contributes to its prevalence in developing countries, including Pakistan. A cross-sectional study was conducted on 650 blood samples taken from suspected patients of HEV in the Rawalpindi cantonment area (Pakistan) from April to November 2019 at the Department of Virology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. Out of them, 444 (68.15%) were male and 206 (31.85%) were female; the detection of anti-HEV IgG antibodies was carried out using a commercial Anti-Hepatitis E virus antibody (IgG) ELISA Kit. The overall anti-HEV IgG prevalence percentages were 19.23% and 4.77% in males and females, respectively. Patients were categorized into eight groups with ages ranging between 1 and 90 years. HEV IgG seroprevalence was the highest in ages 31–40 (6.46%). The study concluded that males aged 40 or above were susceptible and infected with hepatitis E. Full article