Annals of Hepatology
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Annals of Hepatology; doi:10.1016/j.aohep.2020.05.001
The ongoing pandemic of coronavirus disease 2019 (COVID-19) pandemic poses a serious threat to healthcare systems globally. Information regarding to the how the infection affects the liver and relevance of pre-existing liver disease as a risk factor for acquiring the infection or having a severe disease are still scarce. Also, considerations to be considered in liver transplant patients or those having hepatocellular carcinoma or are under immunosuppressive therapy are being matter of analysis as information is being generated. Different treatments for COVID-19 are currently under study some of which may be associated to hepatotoxicity. In the present review we discuss current data on the COVID-19 and liver aiming to provide hepatologists with updated information to face this pandemic.
Annals of Hepatology, Volume 19; doi:10.1016/j.aohep.2019.06.004
Annals of Hepatology, Volume 19, pp 245-250; doi:10.1016/j.aohep.2019.06.007
Studies have suggested that the presence of sarcopenia in patients with cirrhosis could be a predisposing risk factor for hepatic encephalopathy. This systematic review and meta-analysis were conducted to summarize all available evidence on this relationship. A systematic review was carried out in Medline and EMBASE database through December 2018 to identify studies that recruited patients with cirrhosis from any causes and collected data on the presence of minimal or overt hepatic encephalopathy as well as sarcopenia. All study designs (case-control, cohort and cross-sectional studies) were eligible for the meta-analysis. Odds ratio (OR) and 95% confidence interval (CI) were extracted from the included studies and were pooled together using random-effect, generic inverse variance method of DerSimonian and Laird. Five cross-sectional studies with a total of 1,713 patients met our eligibility criteria and were included into the meta-analysis. We found a significantly higher risk of both mild and overt hepatic encephalopathy among cirrhotic patients with sarcopenia when compared with cirrhotic patients without sarcopenia with the pooled OR of 3.34 (95% CI: 1.68-6.67; I2=37%) and 2.05 (95% CI: 1.28-3.29; I2=61%), respectively. This systematic review and meta-analysis demonstrated a significant association between sarcopenia and hepatic encephalopathy among patients with cirrhosis.
Annals of Hepatology, Volume 19, pp 335-337; doi:10.1016/j.aohep.2019.08.003
Shunts between the superior mesenteric vein (SMV) and the right renal vein (RRV) are very rare. Here, we describe and depict the rare case of a liver transplant (LT) in the setting of shunt between SMV and RRV. A 67-year-old white man presenting with Child C cirrhosis secondary to hemochromatosis and persistent encephalopathy was listed for LT. Preoperative abdominal angiotomography revealed the presence of a large spontaneous shunt between the SMV and the RRV. The patient underwent LT by receiving a liver from a 17-year-old brain-dead deceased donor victim of trauma. A large shunt between the SMV and the RRV was confirmed intraoperatively. Although there was no portal vein (PV) thrombosis, the PV was atrophic and had a reduced flow. PV pressure was 22 mmHg (an arterial line was inserted inside the PV stump, and this line was connected to a common pressure transducer, the pressure readings was expressed in the anesthesia monitor). After shunt ligation PV pressure increased to 32 mmHg. There were no post-transplant vascular complications, and the patient was discharged home in good health. Preoperative study of all LT candidates with angio CT scan is mandatory. Whenever there is PV thrombosis, an attempt to remove the entire thrombus is warranted. After thrombectomy or whenever there is not PV thrombosis, all large shunts should be ligated. PV pressure and flow should be measured before and after shunt ligation. In the absence of PV thrombosis, ligation of the shunt should enable an increase in PV flow and pressure, as reported herein.
Annals of Hepatology, Volume 19, pp 238-244; doi:10.1016/j.aohep.2019.09.011
Bacterial infections frequently cause decompensating events in cirrhotic patients and are also the most common factor identified for the development of acute-on-chronic liver failure (ACLF). The increase in the prevalence of infections caused by multidrug-resistant (MDR) microorganisms has resulted in the reduced effectiveness of empiric antimicrobial treatment. We conducted a PubMed search from the last 20 years using the Keywords cirrhosis; multidrug-resistant; infections; diagnosis; treatment; prophylaxis; monitoring; sepsis; nutrition and antibiotic resistant. We made a review about bacterial infections among cirrhotic patients; we mainly focus on the description of diagnostic tools; biomarkers; clinical scores for diagnosis and prognosis also; we made an analysis concerning the monitoring of cirrhotic patients with sepsis and finally made some recommendations about the treatment; prophylaxis and prevention.
Annals of Hepatology, Volume 19, pp 232-237; doi:10.1016/j.aohep.2019.10.005
Preventive effect of metformin in hepatocellular carcinoma (HCC) is not entirely clear. We aimed to evaluate the use of metformin as a protective factor of HCC in diabetic patients. We carried out an electronic search on PUBMED/MEDLINE, Web of Science and LILACS databases, with no limit of date, from April 2017 to January 2019. Eligible studies included cohort and case–control studies. We adressed data about the use of metformin on the risk of HCC development. Two independent reviewers extracted the data. We evaluated the quality of studies by using the Newcastle–Ottawa scale and carried out a meta-analysis using random-effects models. The electronic searches identified 747 studies. After reading abstracts and titles, we excluded 327 duplicated papers and 383 irrelevant references. Eight studies were selected; four case–control and four cohort studies. All studies have observed that the therapy with metformin was associated with a lower risk of HCC, compared with non-metformin therapy. Five articles reported that patients treated with insulin, or insulin secretagogues, presented increased risk of HCC compared to those treated with metformin. One study found that not only statin but also aspirin reduced the risk of HCC, if combined with metformin. A meta-analysis, using the case–control studies, found a combined Odds Ratio of 0.468; 95% CI 0.275–0.799 for the association between HCC and the use of metformin. The use of metformin was associated with a reduced risk of HCC, and it may be a relevant factor for preventing HCC in diabetic patients.
Annals of Hepatology, Volume 19, pp 313-319; doi:10.1016/j.aohep.2019.11.003
Hepatitis B virus (HBV) might be an etiological factor modulating fat distribution in steatotic livers. We aim to compare hepatic steatosis distribution patterns between NAFLD and FL&CHB patients with second-harmonic generation (SHG)/two-photon excited fluorescence (TPEF) method. 42 patients with NAFLD, 46 with FL&CHB and 55 without steatosis were enrolled in the study. Overall and regional steatosis in liver sections were quantified by SHG/TPEF method. The accuracy of which was validated by pathologist evaluation and magnetic resonance spectroscopy (MRS). Difference in degree of overall and regional steatosis between NAFLD and FL&CHB groups was analyzed by Mann–Whitney U test. Multivariable linear regression analysis was used to model factors contributing to steatosis distribution. The hepatic steatosis measured by SHG/TPEF method was highly correlated with pathologist grading (r = 0.83, p < 0.001) and MRS measurement (r = 0.82, p < 0.001). The level of overall steatosis in FL&CHB group is significantly lower than that in NAFLD group (p < 0.001). In NAFLD group, periportal region has significantly lower steatosis percentage than lobule region and overall region (p < 0.001); while in FL&CHB group there is no difference among regions. The ratio of steatosis at periportal region to lobule region is significantly higher in FL&CHB group than that in NAFLD group (p < 0.05). Multivariable linear regression analysis shows that HBV infection is the major contributing factor (β = 0.322, p < 0.01). SHG/TPEF method is an accurate and objective method in hepatic steatosis quantification. By quantifying steatosis in different histological regions, we found steatosis distribution patterns are different between FL&CHB and NAFLD patients.
Annals of Hepatology, Volume 19, pp 295-301; doi:10.1016/j.aohep.2019.12.004
Cases of viral hepatitis reported in Mexico are typically identified as hepatitis A, B and C. However, unspecified cases are reported annually. Hepatitis E virus (HEV) is an emergent agent that causes a self-limiting infection that can evolve to chronic in immunosuppressed individuals. In Mexico, HEV genotype 2 is considered endemic, though it's the prevalence is not well known. Therefore, the present study was designed to determine the prevalence of HEV among patients at the “Hospital Infantil de Mexico Federico Gomez”. The study included 99 patients, anti-HEV antibody (IgG and IgM) were detected by indirect ELISA and viral genome was identified using RT-PCR technique. Two PCR products of positive cases were sequenced. ELISA results were positive in 3% and 6%, for IgG and IgM respectively, 54.5% prevalence was found by PCR. Low lymphocyte count (p < 0.05) and malnutrition (p < 0.005) were significant factors for high PCR prevalence and could increase the possibility of infection. Two samples were sequenced and confirmed the presence of HEV genotype 3. This report reveals the incidence of HEV in pediatric patients in Mexico. Moreover, the identification of HEV genotype 3 in human samples suggests a potential zoonotic risk that requires further research.
Annals of Hepatology, Volume 19, pp 302-312; doi:10.1016/j.aohep.2019.12.003
Hepatic microRNA (miR) expression profiles were explored in aged rats with NAFLD, in order to clarify the molecular mechanisms underlying the pathophysiological processes of aging-related NAFLD. 24 aged rats (18-month-old) and 24 young rats (2-month-old) were randomly divided into two subgroups according to diet, control group and NAFLD group. After 8 weeks of administering 45% high-fat diet or normal diet, total hepatic RNA was extracted from liver tissues of the aged rats. Differentially expressed microRNAs (DE-miRs) in aged NAFLD group were detected and screened out using high-throughput sequencing technology. The data were subjected to Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses using a bioinformatics approach. The sequencing results were further verified by RT-qPCR. Compared with the aged control liver tissues, 6 significantly upregulated miRs (miR-881-3p, miR-871-3p, miR-335, miR-223-3p, miR-155-5p, miR-146b-5p) and 4 significantly downregulated miRs (miR-182, miR-193-3p, miR-31a-5p and miR-96-5p) were identified in the aged NAFLD liver tissues. These DE-miRs were found to be involved in the regulation of cell signaling transduction and metabolism processes, probably affecting signaling pathways relevant to insulin secretion and some senile diseases. RT-qPCR results corroborated the sequencing results and demonstrated that 6 significantly upregulated miRs were not identified in the young group. A total of 10 DE-miRs identified in the aged NAFLD rats were involved in some certain insulin secretion and age-related functional pathways, which may serve as novel candidate targets for the diagnosis and treatment of aging-associated NAFLD.
Annals of Hepatology, Volume 19, pp 320-328; doi:10.1016/j.aohep.2019.11.008
This study aimed to compare the therapeutic efficacy of metformin and other anti-hyperglycemic agents in hepatocellular carcinoma (HCC) patients with type 2 diabetes (T2D). A systematic electronic search on keywords including HCC and different anti-hyperglycemic agents was performed through electronic databases including Medline and EMBASE. The primary outcome was the overall survival (OS). The secondary outcomes were the recurrence-free survival (RFS) and progression-free survival (PFS). Six retrospective cohort studies were included for analysis: Four studies with curative treatment for HCC (618 patients with metformin and 532 patients with other anti-hyperglycemic agents) and two studies with non-curative treatment for HCC (92 patients with metformin and 57 patients with other anti-hyperglycemic agents). Treatment with metformin was associated with significantly longer OS (OR1 yr = 2.62, 95%CI: 1.76–3.90; OR3 yr = 3.14, 95%CI: 2.33–4.24; OR5 yr = 3.31, 95%CI: 2.39–4.59, all P < 0.00001) and RFS (OR1 yr = 2.52, 95%CI: 1.84–3.44; OR3 yr = 2.87, 95%CI: 2.15–3.84; all P < 0.00001; and OR5 yr = 2.26, 95%CI: 0.94–5.45, P = 0.07) rates vs. those of other anti-hyperglycemic agents after curative therapies for HCC. However, both of the two studies reported that following non-curative HCC treatment, there were no significant differences in the OS and PFS rates between the metformin and non-metformin groups (I2 > 50%). Metformin significantly prolonged the survival of HCC patients with T2D after the curative treatment of HCC. However, the efficacy of metformin needs to be further determined after non-curative therapies for HCC patients with T2D.