Cause Of Cirrhosis Research Articles

Discovery of a natural small-molecule AMP-activated kinase activator that alleviates nonalcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is a primary cause of cirrhosis and hepatocellular carcinoma. Unfortunately, there is no approved drug treatment for NASH. AMP-activated kinase (AMPK) is an important metabolic sensor and whole-body regulator. It has been proposed that AMPK activators could be used for treating metabolic diseases such as obesity, type 2 diabetes and NASH. In this study, we screened a marine natural compound library by monitoring AMPK activity and found a potent AMPK activator, candidusin A (CHNQD-0803). Further studies showed that CHNQD-0803 directly binds recombinant AMPK with a KD value of 4.728 × 10–8 M and activates AMPK at both molecular and intracellular levels. We then investigated the roles and mechanisms of CHNQD-0803 in PA-induced fat deposition, LPS-stimulated inflammation, TGF-β-induced fibrosis cell models and the MCD-induced mouse model of NASH. The results showed that CHNQD-0803 inhibited the expression of adipogenesis genes and reduced fat deposition, negatively regulated the NF-κB-TNFα inflammatory axis to suppress inflammation, and ameliorated liver injury and fibrosis. These data indicate that CHNQD-0803 as an AMPK activator is a novel potential therapeutic candidate for NASH treatment.

Fatty Liver Disease, Metabolism and Alcohol Interplay: A Comprehensive Review.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, and its incidence has been increasing in recent years because of the high prevalence of obesity and metabolic syndrome in the Western population. Alcohol-related liver disease (ArLD) is the most common cause of cirrhosis and constitutes the leading cause of cirrhosis-related deaths worldwide. Both NAFLD and ArLD constitute well-known causes of liver damage, with some similarities in their pathophysiology. For this reason, they can lead to the progression of liver disease, being responsible for a high proportion of liver-related events and liver-related deaths. Whether ArLD impacts the prognosis and progression of liver damage in patients with NAFLD is still a matter of debate. Nowadays, the synergistic deleterious effect of obesity and diabetes is clearly established in patients with ArLD and heavy alcohol consumption. However, it is still unknown whether low to moderate amounts of alcohol are good or bad for liver health. The measurement and identification of the possible synergistic deleterious effect of alcohol consumption in the assessment of patients with NAFLD is crucial for clinicians, since early intervention, advising abstinence and controlling cardiovascular risk factors would improve the prognosis of patients with both comorbidities. This article seeks to perform a comprehensive review of the pathophysiology of both disorders and measure the impact of alcohol consumption in patients with NAFLD.

Development and validation of a video-assisted liver biopsy technique using a minimally-invasive device

BackgroundPercutaneous liver biopsy is the gold standard technique for establishing the cause of cirrhosis and liver disease activity assessment. However, some cases of steatohepatitis or other chronic liver diseases show a high number of false negative results in samples obtained via the percutaneous route. This fact justifies performing a liver biopsy via the laparoscopic route. However, this is an expensive technique, with morbidities associated with pneumoperitoneum and anesthetic complications. The main objective of this study is to develop a video-assisted technique that uses only a minimally-invasive device for the liver biopsy and the optical trocar. Without additional trocars, this technique constitutes a less invasive procedure than the existing techniques in clinical practice.MethodsThis is a device development and validation study and patients submitted to abdominal laparoscopic surgery and required liver biopsy for moderate to severe steatosis were recruited. The patients were randomized into two groups: laparoscopic liver biopsy technique (n = 10, control group) and mini-laparoscopic liver biopsy technique (n = 8, experimental group). The times associated with procedure performance in both groups were evaluated using the Mann–Whitney or Kruskal–Wallis tests according to data distribution.ResultsAt baseline, there was no statistical difference regarding gender and type of surgery. The experimental group had a significantly shorter time compared with the group that underwent the traditional procedure in mean procedure time (p = 0.003), biopsy time (p = 0.002) and hemostasis time (p = 0.003).ConclusionsThe mini-laparoscopic biopsy device and technique showed to be capable of safely obtaining sufficient tissue samples, which was minimally invasive and in a shorter time than the classic technique.

Abstract 4605: Chronic VEGF-C signaling exacerbates the progression of non-alcoholic steatohepatitis and hepatocarcinoma through endothelial VEGFR2 and VEGFR3

Abstract Obesity, aging, and metabolic diseases contribute to non-alcoholic fatty liver disease (NAFLD) that can progress to non-alcoholic steatohepatitis (NASH) due to ongoing inflammation and pathological angiogenesis. At present, NASH is a leading cause of cirrhosis, hepatocarcinoma cancer (HCC) and liver transplant within the United States. Pathological angiogenesis of liver sinusoidal endothelial cells (LSECs) is one of the hallmarks of liver injury that disrupt normal LSEC physiology. Therefore, strategies which target factors involved in LSEC dysregulation may improve the progression of hepatic diseases. Examination of a human tissue microarray identified increased levels of vascular endothelial growth factor-C (VEGF-C) in NASH livers compared with healthy individuals. Additionally, single nuclei RNA sequencing and immunofluorescent staining revealed that the receptors for VEGF-C, VEGFR2 and VEGFR3, are primarily expressed by the LSECs. Using murine models of NASH, we further investigated the role of VEGF-C during disease progression. Chronic over expression of VEGF-C by adeno-associated viral (AAV) infection in mice fed a western diet with carbon tetrachloride injections increased NASH progression compared with control AAV infected NASH mice. Interestingly, overexpression of VEGF-C C156S, a variant of VEGF-C which exclusively binds to VEGFR3, resulted in significantly increased hepatic steatosis, but only minimal fibrosis. To determine whether blockade of VEGF-C signaling would delay disease progression, we administered lenvatinib, a tyrosine kinase inhibitor which primarily blocks VEGFR2 and VEGFR3 at low doses, to NASH mice. We discovered that low dose lenvatinib resulted in significantly decreased amount of fibrosis, steatosis, and tumor formation. Analysis of vehicle treated and lenvatinib treated livers by single nuclei RNA sequencing uncovered significant changes in endothelial cell genes associated with extracellular interactions and inflammation, as well as hepatocyte genes involved in lipid synthesis and metabolism. Taken together, these findings indicate that chronic VEGF-C production in NASH plays a role in promoting liver fibrosis and steatosis as well as HCC development, and that blockade of the downstream receptors for VEGF-C, VEGFR2 and VEGFR3, may be a promising therapeutic strategy to mitigate disease severity. Citation Format: Seock-Won Youn, Jason W.-L. Eng, Bhairavi Swaminathan, Pamela Teneqexhi, Rahul Vadakath, Jan K. Kitajewski. Chronic VEGF-C signaling exacerbates the progression of non-alcoholic steatohepatitis and hepatocarcinoma through endothelial VEGFR2 and VEGFR3. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4605.

Current, emerging, and potential therapies for non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) has been identified as the most common chronic liver disease worldwide, with a growing incidence. NAFLD is considered the hepatic manifestation of a metabolic syndrome that emerges from multiple factors (e.g., oxidative stress, metabolic disorders, endoplasmic reticulum stress, cell death, and inflammation). Non-alcoholic steatohepatitis (NASH), an advanced form of NAFLD, has been reported to be a leading cause of cirrhosis and hepatic carcinoma, and it is progressing rapidly. Since there is no approved pharmacotherapy for NASH, a considerable number of therapeutic targets have emerged with the deepening of the research on NASH pathogenesis. In this study, the therapeutic potential and properties of regulating metabolism, the gut microbiome, antioxidant, microRNA, inhibiting apoptosis, targeting ferroptosis, and stem cell-based therapy in NASH are reviewed and evaluated. Since the single-drug treatment of NASH is affected by individual heterogeneous responses and side effects, it is imperative to precisely carry out targeted therapy with low toxicity. Lastly, targeted therapeutic agent delivery based on exosomes is proposed in this study, such that drugs with different mechanisms can be incorporated to generate high-efficiency and low-toxicity individualized medicine.

Research progress on the therapeutic effects of polysaccharides on non-alcoholic fatty liver diseases.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease and is a leading cause of cirrhosis and hepatocellular carcinoma. Due to its complex pathophysiology, there is currently no approved therapy. Polysaccharide, a kind of natural product, possesses a wide range of pharmacological activities. Numerous preclinical studies have confirmed that polysaccharides could interfere with the occurrence and development of NAFLD at multiple interrelated levels, such as improvement of glucose and lipid metabolism, antioxidation, anti-inflammation, and regulation of gut-liver axis, thus showing great potential as novel anti-NAFLD drugs. In this paper, we reviewed the polysaccharides with anti-NAFLD effect in recent years, and also systematically analyzed their possible pharmacological mechanisms.

Mid-Infrared Spectroscopy as a New Tool for Ruling Out Spontaneous Bacterial Peritonitis: A Proof-of-Concept Study.

A highly sensitive and specific point-of-care method for diagnosing spontaneous bacterial peritonitis (SBP) is currently lacking. The objective of the present study is to evaluate the diagnostic value of a rapid, easy-to-use, mid-infrared fiber evanescent wave spectroscopy (MIR-FEWS) method for ruling out SBP. Cirrhotic patients (n = 256) at five centers in France were included for suspected SBP or for the scheduled evacuation of ascites fluid. The mid-infrared spectrum of 7 µL of an ascites fluid sample was recorded using a MIR-FEWS system. To define a model for the diagnosis of SBP, the patients were divided into a calibration group (n = 170) and a validation group (n = 86). Most of the patients were male (71%). The mean age was 60.25 years. Alcohol-related liver disease was the most common cause of cirrhosis. SBP was observed in 18% of the patients. For the diagnosis of SBP in the calibration and validation groups, respectively, the model gave areas under the receiver operating characteristic curves of 0.87 and 0.89, sensitivities of 90% and 87%, specificities of 78% and 80%, positive predictive values of 48% and 50%, negative predictive values of 97% and 96%, positive likelihood ratio of 4.09 and 4.35, negative likelihood ratio of 0.13 and 0.16, Youden index of 0.68 and 0.67, and correct classification rates of 80% and 81%. The results of this proof-of-concept study show that MIR-FEWS is a highly sensitive diagnostic method for ruling out SBP. The method warrants further investigation.

Estimating the epidemiology of chronic Hepatitis B Virus (HBV) infection in the UK: what do we know and what are we missing?

Background: HBV is the leading global cause of cirrhosis and primary liver cancer. However, the UK HBV population has not been well characterised, and estimates of UK HBV prevalence and/or incidence vary widely between sources. We aimed to i) extract and summarise existing national HBV prevalence estimates, ii) add a new estimate based on primary care data, and; iii) critique data sources from which estimates were derived. Methods: We undertook a narrative review, searching for national estimates of CHB case numbers in the UK (incorporating incidence, prevalence and/or test positivity data) across a range of overlapping sources, including governmental body reports, publications from independent bodies (including medical charities and non-governmental organisations) and articles in peer-reviewed scientific journals. An alternative proxy for population prevalence was obtained via the UK antenatal screening programme which achieves over 95% coverage of pregnant women. We also searched for diagnoses of HBV in the QResearch primary care database based on laboratory tests and standardised coding. Results: We identified six CHB case number estimates, of which three reported information concerning population subgroups, including number of infected individuals across age, sex and ethnicity categories. Estimates among sources reporting prevalence varied from 0.27% to 0.73%, congruent with an estimated antenatal CHB prevalence of <0.5%.Our estimate, based on QResearch data, suggests a population prevalence of ~0.05%, reflecting a substantial underestimation based on primary care records. Discussion: Estimates varied by sources of error, bias and missingness, data linkage, and "blind spots" in HBV diagnoses testing/registration. The UK HBV burden is likely to be concentrated in vulnerable populations who may not be well represented in existing datasets including those experiencing socioeconomic deprivation and/or homelessness, ethnic minorities and people born in high-prevalence countries. This could lead to under- or over-estimation of population prevalence estimation.Multi-agency collaboration is required to fill evidence gaps.

A256 INCIDENCE OF CIRRHOSIS AMONG RECENT IMMIGRANTS AND REFUGEES TO ONTARIO, CANADA : A POPULATION-BASED COHORT STUDY

Abstract Background The burden of cirrhosis is increasing in North America where a significant proportion of the population (~20%) is comprised of recent immigrants and refugees. However, the incidence of cirrhosis among this population has not been described. Purpose The aim of this study was to describe the incidence of cirrhosis among recent immigrants and refugees to Ontario, Canada stratified by cirrhosis etiology and region of origin and compare incidence rates to those of Canadian-born and long-term residents. Method This is a population-based cohort study from Ontario, Canada from 2000-2017 using healthcare data housed at ICES. Individuals with incident cirrhosis using a 5-year lookback were identified along with cirrhosis etiology using validated algorithms. Recent immigrants and refugees to Ontario (since 1985) and their World Bank region of origin were defined based on linkage to the Immigration, Refugees, and Citizenship Canada’s Permanent Resident database. Adjusted incidence rates of cirrhosis by immigration status, etiology, and region of origin were calculated and differences in rates were compared between recent immigrants and refugees to long-term residents (born in Canada or arriving before 1985) using age and sex adjusted Poisson regression to calculate rate ratios (RR). Result(s) In total, n=25,054 recent immigrants/refugees with incident cirrhosis were identified. 59% were male, median age was 49 years (IQR 39-61), 99% resided in urban areas and 31% resided in neighbourhoods of the lowest income quintile. The most common regions of origin were East Asia and Pacific (n=8,121; 32%), South Asia (n=5,576; 22%), Europe and Central Asia (n=4,454; 18%) and Latin America/Caribbean (n=3,216; 13%). The majority had NAFLD cirrhosis (n=13,972; 55%), followed by HBV (n=4,648; 19%), ALD (n=2,957; 12%), and HCV (n=2,635; 11%). Cirrhosis incidence stratified by etiology varied by region of origin, with HBV highest among the East Asia and Pacific and Sub-Saharan Africa cohort (Figure 1b), HCV among Sub-Saharan Africa and South Asia (Figure 1c), ALD among European/Central Asia and South Asia (Figure 1d), and NAFLD among the Latin America/Caribbean, Middle East/North Africa, and South Asian populations (Figure 1e). When comparing age and sex adjusted incidence of cirrhosis by etiology and immigration status, rates were lower among recent immigrants/refugees for all causes compared to long-term residents (all RR &amp;lt;1.0; Figure 1a,c-f) with the exception of HBV where it was over 4-fold higher (Figure 1b). Image Conclusion(s) Rates of HBV cirrhosis are substantially higher among migrants to Ontario while rates of all other causes of cirrhosis are lower, likely explained by the healthy immigrant effect. NAFLD has emerged as the most common etiology of cirrhosis among migrants with rates approaching those of Canadian-born and long-term residents. These data add to our understanding of the evolving epidemiology of cirrhosis and the contribution of other etiologies outside of viral hepatitis among immigrants. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Lipid Profile as an Indicator of Severity in Cirrhosis of Liver: Hospital based Cross-sectional Study.

Various scoring systems are available to assess the severity of cirrhosis, that is, the Child-Pugh score and Model for End-Stage Liver Disease (MELD) score. Since the liver is the major site for converting excess carbohydrates into various lipids, the deranged lipid profile can act as a prognostic biomarker of cirrhosis. We assessed the lipid profile abnormalities among patients with cirrhosis of the liver and correlated them with the severity of cirrhosisMaterials and methods: This is an analytical cross-sectional study on lipid profile as an indicator of severity in cirrhosis of the liver among patients admitted to the medical ward of a tertiary care teaching hospital in Tamil Nadu. Following detailed investigation and confirmation of cirrhosis, a fasting serum lipid profile was measured in all eligible patients with cirrhosis. Total serum cholesterol, triglyceride (TGL), and high-density lipoprotein (HDL) were measured by direct method and serum low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) were calculated by using the Friedwald formulaResults: A total of 120 patients were studied. Of them, 76 (63%) were male. Of them, alcohol (84, 75.0%), hepatitis B (8, 7.1%), and nonalcoholic steatohepatitis (NASH) (6, 5.4%) were the most common cause of cirrhosis. A clear dose-response relationship (decreasing trend) is seen in the levels of lipids for increasing severity based on the Child-Pugh score and MELD score (except for a score of ≤10). Further, the cholesterol, LDL, and HDL were significantly lower among patients with ascites or with spontaneous bacterial peritonitis compared to their respective groups. However, none of the lipid profiles significantly differed based on the presence of upper gastrointestinal (UGI) bleeding Conclusion: This study observed that there is a significant reduction in levels of lipid profile parameters like serum total cholesterol, LDL, VLDL, TGL, and HDL in patients with cirrhosis as the severity increases. Further formulation of the scoring system in association with a preexisting scoring system may provide a better assessment of patients' prognosis in view of morbidity and mortality. We recommend it is necessary to assess the fasting lipid profile in all patients with cirrhosis and prognosticate their disease progression.

Impact of COVID-19 fear on Hepatitis C management

Background/Aim: Hepatitis C virus (HCV) infection, a major cause of cirrhosis worldwide, is the most common cause of cirrhosis and hepatocellular carcinoma in Turkey. Today, HCV infection can be treated effectively and safely using direct-acting antiviral drugs, and therefore, the World Health Organization has announced elimination targets by 2030. During the pandemic, many social and personal restrictions were applied for fear of increasing the prevalence of coronavirus disease 2019 (COVID-19) infection. Here we investigate the effects of these restrictions on managing HCV infection in internal medicine departments that deal with both infections. Methods: Patients who applied to the internal medicine departments of our hospital and tested for anti-HCV between 11 March 2020 and 09 April 2022, which was the time interval when official restrictions were applied in Turkey during the COVID-19 pandemic, were included in the study. Patients who were not tested for anti-HCV were excluded from the study. The study was planned as a retrospective cohort study, and patients’ files tested for anti-HCV were scanned. Anti-HCV positivity, HCV RNA PCR testing, and treatment status in HCV RNA-positive patients were evaluated. Results: During the official pandemic period when social restrictions were applied, anti-HCV positivity was revealed in 400 (1.9%) of 21,501 patients for whom anti-HCV tests were performed in internal medicine departments. HCV RNA was not tested in 64 of 400 patients with positive anti-HCV test (16%), and 83 (24.7%) of 336 patients tested for HCV RNA were found to be positive. It was determined that 17 (20.5%) of the HCV RNA-positive patients did not receive antiviral treatment. Conclusion: In studies conducted in Turkey in the pre-pandemic period, it was determined that HCV RNA was not tested in approximately half of the anti-HCV-positive patients, while this rate was found to be only 16% during the pandemic period. This can be explained by the fact that patients infected with the COVID-19 virus were mostly followed-up by internal medicine clinics, where the awareness of viral hepatitis was high. It was determined that 20.5% of the patients with positive HCV RNA PCR tests remained untreated. This finding suggested that the social and personal restrictions applied during the pandemic led to patient follow-up and treatment disruptions.

An Echocardiographic Evaluation of Cardiopulmonary Evaluation of Cardiopulmonary Functions in Patients with Cirrhosis of Liver and Correlation with Severity of Disease

BACKGROUND Cirrhosis is the end result of varieties of chronic liver disease. A large proportion of patients with cirrhosis develop cardiopulmonary complication. The aim of this study was to evaluate the cardiopulmonary functions of patient with cirrhosis of liver and to correlate these abnormalities with CTP and MELD score.&#x0D; METHODS The study involved 81 cirrhotic patients admitted in Department of Gastroenterology of TUTH over a period of one year. The diagnosis of cirrhosis was established and clinical evaluation and investigation done.&#x0D; RESULTS The mean age of cirrhotic patients included in the study was 52 years. Alcohol was most common cause of cirrhosis (75.31%). The mean CTP score and MELD score was 10.02±1.77 and 23.59±7.53 respectively. Thirty patients (37.03%) had prolonged QTc interval, which had statistically significant association with alcohol as etiology of cirrhosis (p = 0.04). More than half (50.62%) of patients had diastolic dysfunction but it was not statistically significantly associated with CTP and MELD-Na score. Seven patients had evidence of intrapulmonary shunting, which had statistically significant association with MELD-Na score (p =0.01). Similarly, total 5 patients (6.17%) had PPHTN but there was no statistically significant association with CTP and MELD-Na score. Seventeen patients had dilated left atrium with no statistically significant association with CTP score and MELD-Na score.&#x0D; CONCLUSION There was significant incidence of cardiopulmonary abnormalities in cirrhotic patients. Every patient with decompensated cirrhosis irrespective of severity of disease should be evaluated for cardiopulmonary complication with a noninvasive, real-time, rapid imaging transthoracic contrast echocardiography.

Safety and Efficacy of Atezolizumab-Bevacizumab in Real World: The First Indian Experience

Atezolizumab-bevacizumab (atezo/bev) combination is a recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC). There are no studies from India reporting the safety and efficacy of this drug in real-world settings where most patients present in an advanced stage. In this retrospective study from two centers in India, we included patients with uHCC who received atezo/bev as first-line systemic therapy. Comparison of overall survival (OS) among the different Child-Turcotte-Pugh (CTP) classes was the primary objective, while progression-free survival (PFS), radiologic response, and adverse events to the therapy were secondary objectives. The median age of the 67 patients who received atezo/bev therapy was 61 (29-82) years, and 86% were males. Nonalcoholic steatohepatitis (55.2%) was the commonest cause of cirrhosis, and most patients belonged to BCLC-C (74.6%%). There were 24 patients in CTP A, 36 in CTP B, and 7 in CTP C. The median OS was 12 (95%CI, 8.16-15.83) months in the cohort. The median OS in CTP class A, B, and C was 21 (95%CI, 0-42.06) months, 9 (95%CI, 5.46-12.53) months, and 4 (95%CI, 2.14-5.85) months, respectively (P < 0.001). The median PFS in the whole cohort was 8 (95%CI, 6.03-9.96) months. The median PFS in Child A, B, and C was 18 (95%CI, 0.16-35.84) months, 8 (95%CI, 6.14-9.85) months, and 2 (95%CI, 1.77-2.23) months (P < 0.001). On mRECIST evaluation, 12.9% had achieved a complete response, 25.8% had a partial response, 27.41% had stable disease, and the rest had progressed. The objective response rate was 38.7%, and the disease control rate was 66.12%. Of the 64% who developed adverse events, 13.43% discontinued the drug. The incidence of grade ≥3 events was significantly higher in CTP C (85.7%) compared to CTP A (12.5%) and CTP B (14%) (P < 0.001). Atezolizumab-bevacizumab is safe and effective in uHCC inreal-world settings. Candidate selection is of utmost importance in treating uHCC with atezolizumab-bevacizumab to achieve a good response. Current evidence strongly suggests limited use of atezolizumab-bevacizumab in patients with CTP C, and such individuals should not be considered for this combination therapy.

Etiologies of cirrhosis by ethnicities of patients with hepatocellular carcinoma.

515 Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. While there are several factors that can impact patient outcomes, ethnicity remains a major contributor towards disease incidence and the expected clinical course. There are various etiologies that can lead to the development of HCC among different ethnic groups, though further studies are required to identify the most pertinent risk factors in recent years. Methods: This was a single center, retrospective study in HCC patients to identify differences in cirrhosis etiologies based on ethnicity. All patients were diagnosed with HCC between March 2014 and April 2022. Possible causes of cirrhosis included alcohol, hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and other chronic liver disease. Results: A total of 276 patients were included in this study. For ethnic background, there were 97 Latino, 97 White, 50 Asian, 16 Black, and 16 patients of other ethnicities. With regards to significant differences in the etiologies of cirrhosis, 58 patients (59.8%) of White ethnicity were found to have cirrhosis related to HCV compared to 71 patients (39.7%) of all other ethnic groups (p = 0.002). In addition, when comparing Latino to non-Latino patients, there was a greater proportion of patients with cirrhosis due to NAFLD (24.7% vs 10.1%, p = 0.002) and cirrhosis from alcohol consumption (24.7% vs 10.1%, p = 0.002). HBV also varied significantly by ethnicity with 16 Asian patients (32%) found to have HBV cirrhosis compared to 5 patients (2.2%) of other ethnic groups (p &lt;0.001). See table for additional details. Conclusions: Our study demonstrates significant differences in the cirrhosis etiologies of HCC patients depending on ethnicity. With the incidence and mortality rates of HCC continuing to rise worldwide, it is important for clinicians to be aware of these differences so that the appropriate preventative measures can be pursued.[Table: see text]

Liver Cirrhosis among Young Adults Admitted to the Department of Gastroenterology in a Tertiary Care Centre: A Descriptive Cross-sectional Study

Cirrhosis in young adults is an important health problem worldwide and is a common disease. Patients usually present late in a decompensated state with varied complications. However, national data on the exact burden of the disease is lacking. The aim of this study was to find out the prevalence of liver cirrhosis among young adults admitted to the Department of Gastroenterology in a tertiary care centre. A descriptive cross-sectional study was done among patients admitted to the Department of Gastroenterology in a tertiary care centre between 25 November 2021 to 30 November 2022 after receiving ethical approval from the Institutional Review Committee [Reference number: 227(6-11)E2-078/079]. Convenience sampling was done. Point estimate and 95% Confidence Interval were calculated. Among 989 patients, liver cirrhosis in young adults was seen in 200 (20.22%) (18.12-22.32, 95% Confidence Interval). Chronic alcohol use was the primary cause of cirrhosis seen in 164 (82%) cases. The most typical presenting symptom was abdominal distension seen in 187 (93.50%) patients. The most frequent complication was ascites seen in 184 (92%) patients. The most frequent endoscopic finding was gastro-oesophagal varices seen in 180 (90%) patients. There were 145 (72.50%) men and 55 (27.50%) women. The prevalence of liver cirrhosis in young adults was found to be lower than the other studies done in similar settings. ascites; liver cirrhosis; prevalence.

A rare case of Flood syndrome in emergency department: A case report and review of recent reported cases

Introduction:Flood syndrome is a rare and potentially fatal complication of liver cirrhosis with gross ascites.Case presentation:We present a case of Flood syndrome in a gentleman with alcoholic cirrhosis and ascites who had sudden spontaneous rupture of umbilical hernia, resulting in sudden gush of ascitic fluid from the hernia. The wound was cleaned and covered in sterile dressing and was admitted for further management. His umbilical hernia wound was closed at bedside by General Surgery team and he underwent ultrasound‐guided ascitic drain insertion by Interventional Radiology. His stay was complicated by bacterial peritonitis which was treated with intravenous antibiotic. Patient eventually recovered and was discharged well.Discussion:Flood syndrome has high complication and mortality rate. Recent reported cases were reviewed, focusing on the causes of cirrhosis, complications of Flood syndrome, treatments provided and the outcomes.Conclusion:There is currently no standard guideline for the management of Flood syndrome which falls in the grey area between medical and surgical management. Proper medical management with early surgical consultation is important to reduce the morbidity and mortality for these patients.

Diagnostic Validity of Leucocyte Esterase Dipstick Tests for Spontaneous Bacterial Peritonitis in Patients with Cirrhosis

Background: One of the worst sequelae of cirrhosis and ascites is spontaneous bacterial peritonitis (SBP). Early detection and treatment of SBP are therefore essential for survival because this complication is linked to a high death risk if antibiotics are not administered promptly. Leukocyte esterase dipstick testing can identify the SBP quickly. Objective: To evaluate the diagnostic accuracy of leucocyte esterase dipstick test for the detection of spontaneous bacterial peritonitis taking ascitic fluid neutrophil count as gold standard. Study Design: Cross Sectional Study Settings: Department of Gastroenterology, Lady Reading Hospital, Peshawar Study Duration: This study was conducted from 1st July 2021 till 30th June 2022 Materials and Methods: Two samples (10cc each) of ascitic fluid aspirate were obtained from patients with cirrhosis on admission to the hospital, presenting with ascites, fever and abdominal pain. Bedside leucocyte esterase dipstick test was performed on one sample and the other was sent to hospital laboratory for ascitic fluid analysis for neutrophil count. The results of both modalities were compared diagnostic accuracy which was recorded in terms of sensitivity, specificity, positive predictive value and negative predictive. Results: Mean age of the patients was 46.68 ± 10.239 years. A total of 170 patients were enrolled. Age of the patients ranged from 18 to 75 years. Male patients were 113 (66.5%) while 57 patients (33.5%) were female. Hepatitis C was the leading cause of cirrhosis observed in 89 patients (52.4%). The sensitivity, specificity, positive and negative predictive value of leucocyte esterase dipstick test observed were 89.7%, 96.2%, 87.5% and 96.9% respectively. Conclusion: Leucocyte esterase dipstick test is a convenient, inexpensive and rapid diagnostic modality for SBP with better diagnostic accuracy. Keywords: Spontaneous Bacterial Peritonitis, Leucocyte Esterase Dipstick test, Diagnostic Accuracy.

Midodrine versus Albumin to Prevent Paracentesis Induced Circulatory Dysfunction in Acute on Chronic Liver Failure Patients in the Outpatient Clinic–a Randomized Controlled Trial

Paracentesis-induced circulatory disturbance (PICD) occurs in 12-20% of patients receiving human albumin for large-volume paracentesis, and can occur at lower than five liter paracentesis in acute-on-chronic liver failure (ACLF). Albumin infusions are associated with higher costs and more prolonged daycare admissions. The aim of the study was to determine if oral midodrine-hydrochloride can prevent PICD in these patients by increasing the mean arterial pressure (MAP). This open-labeled randomized controlled trial included ACLF patients undergoing paracentesis between 3 and 5L, who were randomized to receive either 20% human albumin or midodrine hydrochloride 7.5mg thrice daily for three days, 2h before paracentesis. MAP was recorded daily. The primary outcome was the plasma renin activity (PRA) on day six, and a 50% increase from baseline was considered PICD. 183 consecutive patients of ACLF were screened, and 50 patients were randomized to either arms. Alcohol was the most common underlying cause of cirrhosis. On day 6, PRA was non-significantly (P=0.056) higher in the midodrine group. The absolute change of PRA between the two groups was not significant (P= 0.093). Four (16%) patients in the albumin group and five (20%) in the midodrine group developed PICD. MAP increase was not different between the albumin and midodrine arms (P= 0.851). Midodrine was found to be more cost-effective. Three days of oral midodrine is as effective as a human-albumin infusion in preventing PICD in ACLF patients undergoing paracentesis lesser than that done in large volume paracentesis.

Caspase-11 promotes high-fat diet-induced NAFLD by increasing glycolysis, OXPHOS, and pyroptosis in macrophages.

Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of 25% of the population and is a leading cause of cirrhosis and hepatocellular carcinoma. NAFLD ranges from simple steatosis (non-alcoholic fatty liver) to non-alcoholic steatohepatitis (NASH). Hepatic macrophages, specifically Kupffer cells (KCs) and monocyte-derived macrophages, act as key players in the progression of NAFLD. Caspases are a family of endoproteases that provide critical connections to cell regulatory networks that sense disease risk factors, control inflammation, and mediate inflammatory cell death (pyroptosis). Caspase-11 can cleave gasdermin D (GSDMD) to induce pyroptosis and specifically defends against bacterial pathogens that invade the cytosol. However, it's still unknown whether high fat diet (HFD)-facilitated gut microbiota-generated cytoplasmic lipopolysaccharides (LPS) activate caspase-11 and promote NAFLD. To examine this hypothesis, we performed liver pathological analysis, RNA-seq, FACS, Western blots, Seahorse mitochondrial stress analyses of macrophages and bone marrow transplantation on HFD-induced NAFLD in WT and Casp11-/- mice. Our results showed that 1) HFD increases body wight, liver wight, plasma cholesterol levels, liver fat deposition, and NAFLD activity score (NAS score) in wild-type (WT) mice; 2) HFD increases the expression of caspase-11, GSDMD, interleukin-1β, and guanylate-binding proteins in WT mice; 3) Caspase-11 deficiency decreases fat liver deposition and NAS score; 4) Caspase-11 deficiency decreases bone marrow monocyte-derived macrophage (MDM) pyroptosis (inflammatory cell death) and inflammatory monocyte (IM) surface GSDMD expression; 5) Caspase-11 deficiency re-programs liver transcriptomes and reduces HFD-induced NAFLD; 6) Caspase-11 deficiency decreases extracellular acidification rates (glycolysis) and oxidative phosphorylation (OXPHOS) in inflammatory fatty acid palmitic acid-stimulated macrophages, indicating that caspase-11 significantly contributes to maintain dual fuel bioenergetics-glycolysis and OXPHOS for promoting pyroptosis in macrophages. These results provide novel insights on the roles of the caspase-11-GSDMD pathway in promoting hepatic macrophage inflammation and pyroptosis and novel targets for future therapeutic interventions involving the transition of NAFLD to NASH, hyperlipidemia, type II diabetes, metabolic syndrome, metabolically healthy obesity, atherosclerotic cardiovascular diseases, autoimmune diseases, liver transplantation, and hepatic cancers.

Effectiveness of Proton Pump Inhibitor Therapy in the Prevention of Bleeding After Prophylactic Endoscopic Variceal Band Ligation.

Background Endoscopic variceal ligation (EVL) is a surgical intervention that can work well to curb variceal bleeding in people with liver cirrhosis. However, it could make ulcer bleeding worse and be fatal in some cases. The widespread use of proton pump inhibitors (PPI) in cirrhotic individuals with variceal bleeding is empirical rather than based on scientific data. According to many studies, PPIs reduce the size of post-EVL ulcers. This study aimed to see if PPI use could reduce rebleeding after endoscopy therapy in cirrhotic patients with variceal bleeding. Methodology A retrospective cross-sectional study was conducted at a tertiary care hospital from August 2019 to September 2021. Cirrhotic patients with bleeding gastroesophageal varices(GEVs) who had undergone EVL at the same hospital were enrolled in the study. Medical records were organized, and the sample was divided into two groups based on whether or not PPI was given. Both PPI and non-PPI patients had their endoscopic findings, initial hemostasis outcomes, rebleeding rates, bleeding-related mortality rates, and treatment-related comorbidities compared. Results A total of 46 patients were selected for the study and divided into two groups (PPI group n=28 and non-PPI group n=18). The majority of the patients were males. The PPI group had a mean age of 58.6 ±7.8 years, whereas the non-PPI group had a mean age of 53.6 ±4.4 years. Hepatitis B virus (HBV) infection was the most prevalent cause of cirrhosis in both groups. After endoscopic treatment, three patients (16%) in the non-PPI group suffered a variceal hemorrhage. Bleeding-related fatalities and the time it took for the bleeding to stop varied significantly between the two groups. History of variceal bleeding (relative risk (RR)=1.45; 95% confidence interval (CI), 1.60-7.67; p=0.02), presence of gastric varices (RR=2.23; 95% CI, 2.56-9.832; p=0.035), and not administering PPIs (RR =7.542; 95% CI, 3.98-29.13; p=0.008) were linked with rebleeding. The presence of red concurrent esophageal varices (RR=6.37; 95% CI, 0.562-15.342; p=0.002) and failure to provide PPIs (RR=2.3; 95% CI, 1.621-25.64; p=0.04) were linked with post-EVL bleeding in a multivariate analysis. Conclusions Proton pump inhibitors reducethe occurrence of early bleeding and adverse events after EVL in cirrhotic patients. Not prescribing PPIs and the presence of GEVs were substantially related to a higher risk of bleeding during preventative EVL. Not initiating PPI medication immediately was the sole predictor of bleeding complications in patients who had undergone EVL without gastric varix treatment. To lower the risk of post-EVL ulcer bleeding, we recommend PPI use in patients undergoing EVL.