Severe Alcoholic Hepatitis Research Articles

P218 Association of HLA-DRB1*04 with acute severe hepatitis of unknown aetiology in children: Results from an Irish cohort

P218 Association of HLA-DRB1*04 with acute severe hepatitis of unknown aetiology in children: Results from an Irish cohort

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2022.

For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable diseases. In this report, we describe the results of thirteen such studies surveyed by the APSU in 2022, including reported case numbers and incidence estimates, demographics, clinical features, management and short-term outcomes. Conditions described are: acute flaccid paralysis (AFP); congenital cytomegalovirus (cCMV); neonatal and infant herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV) and paediatric HIV infection; severe complications of influenza; juvenile-onset recurrent respiratory papillomatosis (JoRRP); congenital rubella infection/syndrome; congenital varicella syndrome (CVS) and neonatal varicella infection (NVI); and the new conditions dengue; Q fever; and severe acute hepatitis. In 2022, cases of severe complications of influenza were reported to the APSU for the first time since 2019. This likely reflects the easing of government-mandated restrictions imposed in 2020-2021 to curb the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the re-emergence of a range of infectious diseases. As previously, AFP surveillance by the APSU contributed to Australia achieving a minimum target incidence of one AFP case per 105 children aged less than 15 years. Cases of JoRRP and NVI were reported in 2022. This indicates potential gaps in human papillomavirus (HPV) and varicella vaccination coverage respectively, especially in high-risk groups such as young migrant and refugee women of childbearing age from countries without universal vaccination programs. Paediatric HIV case numbers resulting from mother-to-child-transmission (MTCT) of HIV remain low in Australia due to use of effective intervention strategies. However, there has been an increase in the number of imported cases of HIV in children (mainly perinatally-acquired) from countries with a high HIV prevalence. Without effective vaccines, there has been no decline in the incidence of congenital CMV and neonatal HSV, indicating the importance of early identification and management to reduce morbidity and mortality. The first cases of dengue, Q fever and severe acute hepatitis were received by APSU in 2022, including two cases of acute hepatitis in which aetiology has not been confirmed to date. The APSU has an important ongoing role in monitoring rare childhood infections.

Alcoholic hepatitis - current and future treatment approaches

Acute severe alcoholic hepatitis is a serious disease with poor prognosis. As a result of an improved understanding of the underlying pathomechanisms, a variety of new, innovative therapeutic modalities are currently being investigated that may help to improve prognosis. New approaches include the application of anti-inflammatory agents (e.g., interleukin-1 inhibitors), modifications of the gut-liver axis via fecal microbiome transfer or the administration of non-absorbable antibiotics (e.g., rifaximin), and drugs to enhance hepatocellular regeneration (e.g., interleukin-22 agonists). This article describes current management concepts of alcoholic hepatitis and provides an overview of new potential treatment approaches.

Management of alcoholic hepatitis: A clinical perspective.

Alcohol-associated liver disease is the primary cause of liver-related mortality worldwide and one of the most common indications for liver transplantation. Alcoholic hepatitis represents the most acute and severe manifestation of alcohol-associated liver disease and is characterized by a rapid onset of jaundice with progressive inflammatory liver injury, worsening of portal hypertension, and an increased risk for multiorgan failure in patients with excessive alcohol consumption. Severe alcoholic hepatitis is associated with a poor prognosis and high short-term mortality. During the COVID-19 pandemic, rates of alcohol-associated hepatitis have increased significantly, underscoring that it is a serious and growing health problem. However, adequate management of alcohol-associated hepatitis and its complications in everyday clinical practice remains a major challenge. Currently, pharmacotherapy is limited to corticosteroids, although these have only a moderate effect on reducing short-term mortality. In recent years, translational studies deciphering key mechanisms of disease development and progression have led to important advances in the understanding of the pathogenesis of alcoholic hepatitis. Emerging pathophysiology-based therapeutic approaches include anti-inflammatory agents, modifications of the gut-liver axis and intestinal dysbiosis, epigenetic modulation, antioxidants, and drugs targeting liver regeneration. Concurrently, evidence is increasing that early liver transplantation is a safe treatment option with important survival benefits in selected patients with severe alcoholic hepatitis not responding to medical treatment. This narrative review describes current pathophysiology and management concepts of alcoholic hepatitis, provides an update on emerging treatment options, and focuses on the need for holistic and patient-centred treatment approaches to improve prognosis.

Effects of coenzyme Q10 and N-acetylcysteine on experimental poisoning by paracetamol in Wistar rats.

Paracetamol (PAR) is a drug widely used in human and veterinary medicine as an analgesic and antipyretic, often involved in cases of intoxication. The most common clinical signs result from damage to red blood cells and hepatocytes, and this intoxication is considered a model for the induction of acute liver failure. In the present study, the hepatoprotective effects of coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC) against experimental paracetamol (PAR) poisoning were analysed. Thirty-five adult Wistar rats (Rattus novergicus albinus) were randomly assigned to five groups, and thirty-one of these survived the treatments. Negative control group (CON-) received 1mL of 0.9% NaCl orally (PO). Other groups received 1.2g/kg of PAR (PO). Positive control group (CON+) received only PAR. NAC group received 800 mg/kg intraperitoneally (IP) of NAC 1h after the administration of PAR and at 12 h received 1mL of 0.9% NaCl, IP. The fourth group (CoQ10) received 1h and 12 h after intoxication, CoQ10 (10mg/kg IP). And the fifth group (NAC+CoQ10) received NAC (800mg/kg, IP) and CoQ10 (10mg/kg, IP). After 12 hours, the rats were euthanized and necropsied to collect liver and kidney tissues for histopathological evaluation and electronic microscopy. A single dose of PAR caused severe acute hepatitis. NAC couldn't reverse the liver and kidney damages. The group that received CoQ10 and NAC had moderate liver damage, while the group that received only CoQ10 had lower values of liver enzymes and mild liver and kidney damage. Animals that received treatment with CoQ10 or NAC+CoQ10 presented normal hepatocyte mitochondria and nuclei. Although CoQ10 couldn't reverse PAR organ damage, results indicate promising hepatoprotection in Wistar rats.

Value of inflammatory response and oxidative damage in the diagnosis of infections in severe alcoholic hepatitis

Severe alcoholic hepatitis is the most lethal complication in alcohol dependent patients. The concurrence of infections in these patients is very frequent. Both produce a systemic inflammatory response syndrome (SIRS), secondary to intense release of inflammatory cytokines, which can complicate the diagnosis. In our study, Interleukin (IL)-6 and IL-10 levels are higher in patients with SIRS (p<0.001 and p = 0.033, respectively). IL-4, IL-6, Interferon‐gamma (IFNγ), Tumor necrosis factor alpha (TNFα) and IL-17 levels correlate with liver function, as estimated by MELD-Na (p = 0.018, p = 0.008, p = 0.009, p = 0.016 and p = 0.006, respectively). Malondialdehyde (MDA), a product of lipid peroxidation and marker of cell damage, also correlates with liver function (p = 0.002), but not with SIRS or infections. Only elevated IL-6 correlates independently with the presence of infections (RR=1.023 IC 95% 1.000–1.047), so it may be useful for the correct diagnosis in these patients. Values greater than 30 pg/mL have a sensitivity: 86.7% and specificity: 94.7% for the diagnosis of infections.

A multicenter double-blind, placebo-controlled randomized trial to evaluate the safety and efficacy of bovine colostrum in the treatment of severe alcoholic hepatitis (SAH)

BackgroundSevere alcoholic hepatitis (SAH) is associated with high mortality. Numerous studies and meta-analysis have reported that corticosteroids reduce the 28-day mortality in SAH, but not the 6-month mortality. Therefore, newer treatments for SAH need to be studied. A pilot study from our group had recently treated ten patients with SAH with bovine colostrum (BC) [20 g thrice in a day for 8 weeks] and prednisolone. This therapy improved the biological functions and 3-month mortality. However, as more and more data showed the failure of corticosteroids to improve the 3- and 6-month mortality, especially in patients with high mDF and MELD scores, we planned this trial to study the safety and efficacy of BC (without corticosteroids) in the treatment of SAH.MethodThis is a multicenter, parallel, double-blind, randomized (1:1) placebo-controlled trial, which will enroll 174 patients with SAH from 5 academic centers in the India. Patients will receive freeze-dried BC or placebo by random 1:1 allocation for 4 weeks. The primary outcome measure is survival at 3 months. The secondary outcome measures are survival at 1 month, change in mDF and MELD scores, change in endotoxin and cytokines (alpha TNF, IL6, and IL8) levels, number of episodes of sepsis [pneumonia, spontaneous bacterial peritonitis (SBP), cellulitis, urinary tract infection (UTI)] from baseline to 4 weeks.DiscussionThis study will evaluate the safety and efficacy of bovine colostrum in improving the survival of patients with SAH.Trial registrationClinicalTrials.gov NCT02473341. Prospectively registered on June 16, 2015.

Novel Microbial Signatures in the Faecal Microbiome Associated with Severe Alcoholic Hepatitis: Bacteroides Finegoldii and Veillonella Dispar

Background: Alcoholic hepatitis is associated with dysbiosis, resulting in compositional changes in the gut microbiome, endotoxin transfer to the portal vein, and activation of inflammatory signalling pathways in the liver. However, the microbiome signature of severe alcoholic hepatitis (AH) patients of Indian origin is unknown. Aim: To investigate the microbiome diversity of Indian AH patients in comparison to non-alcoholic healthy controls (HC). Methods: 16S rRNA amplicon-based metagenomics analysis of faecal samples at the time of AH diagnosis (n=12) was compared with HC (n=6), and correlation with survival status, co-occurrence networking, Linear Discriminant Analysis Effect Size (LEfSe), and the relationship between diet – microbiome were performed. Results: 16S rDNA data showed a significant abundance of the Enterobacteriaceae family belonging to the phylum Proteobacteria and a depletion of the phylum Firmicutes in AH. A species-level classification identified Klebsiella pneumonia, Klebsiella variicola, and Parabacteroides distasonis as having the highest predictive performance value with reference to mortality at 60 days. Apart from this, a unique finding was the abundance of Bacteroides finegoldii and Veillonella dispar in AH patients. Moreover, the co-occurrence networking analysis revealed a higher level of connectivity and complexity within the microbial community of AH patients compared to HC. Thus, indicating the significant positive association (Spearman r &gt; 0.7, p &lt; 0.01) among members of the Firmicutes, Bacteroidetes, and Proteobacteria phyla in AH. Wilcoxon-Rank Sum test (p &lt; 0.01) identified Firmicutes phyla occurrence associated with high carbohydrate intake and Actinobacteria phyla with low protein intake. Conclusion: The findings provide the baseline occurrence profile of the gut microbiome signature of liver damage and the diet-microbiome relationship in patients with severe AH. The study demonstrated an abundance of Proteobacteria phyla, indicating their role in inflammatory conditions, and further identified Bacteroides finegoldii and Veillonella dispar in severe AH patients. Additionally, Klebsiella pneumonia, Klebsiella variicola, and Parabacteroides distasonis were identified as mortality-predictive risk biomarkers.

Hepatic graft-versus-host disease: what we know, when to biopsy, and how to diagnose

Graft-versus-host disease (GVHD) is one of the serious complications that may develop after hematopoietic cell transplantation (HCT), for hematologic malignancies, solid organ transplantation, and other hematologic disorders. GVHD develops due to T lymphocytes present in the graft attacking the host antigens, which results in tissue damage. A significant number of HCT patients develop acute or chronic GVHD, which may affect multiple organs including the liver. The diagnosis of hepatic GVHD (hGVHD) is challenging as many other conditions in HCT patients may lead to liver dysfunction. Particularly challenging among the various conditions that give rise to liver dysfunction is differentiating sinusoidal obstruction syndromeand drug-induced liver injury (DILI) from hGVHD on clinical grounds and laboratory tests. Despite the minimal risks involved in performing a liver biopsy, the information gleaned from the histopathologic changes may help in the management of these very complex patients. There is a spectrum of histologic features found in hGVHD, and most involve histopathologic changes affecting the interlobular bile ducts. These include nuclear and cytoplasmic abnormalities including dysmorphic bile ducts, apoptosis, and cholangiocyte necrosis, among others. The hepatitic form of hGVHD typically shows severe acute hepatitis. With chronic hGVHD, there is progressive bile duct loss and eventually fibrosis. Accurate diagnosis of hGVHD is paramount so that timely treatment and management can be initiated. Techniques to prevent and lower the risk of GVHD from developing have recently evolved. If a diagnosis of acute GVHD is made, the first-line of treatment is steroids. Recurrence is common and steroid resistance or dependency is not unusual in this setting. Second-line therapies differ amonginstitutions and have not been uniformly established. The development of GVHD, particularly hGVHD, is associated with increased morbidity and mortality.

Signatures of AAV-2 immunity are enriched in children with severe acute hepatitis of unknown etiology.

Severe acute hepatitis of unknown etiology in children is under investigation in 35 countries. Although several potential etiologic agents have been investigated, a clear cause for the liver damage observed in these cases remains to be identified. Using VirScan, a high-throughput antibody profiling technology, we probed the antibody repertoires of nine cases of severe acute hepatitis of unknown etiology treated at Children's of Alabama and compared their antibody responses with 38 pediatric and 470 adult controls. We report increased adeno-associated dependoparvovirus A (AAV-A) breadth in cases relative to controls and adeno-associated virus 2 (AAV-2) peptide responses that were conserved in seven of nine cases but rarely observed in pediatric and adult controls. These findings suggest that AAV-2 is a likely etiologic agent of severe acute hepatitis of unknown etiology.

Clinical Characteristics of Genuine Acute Autoimmune Hepatitis

Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74–100] vs. 61% [10–100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8–23] vs. 16.5 [15–17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.

The Elk-3 target Abhd10 ameliorates hepatotoxic injury and fibrosis in alcoholic liver disease

Alcoholic liver disease (ALD) and other forms of chronic hepatotoxic injury can lead to transforming growth factor β1 (TGFβ1)-induced hepatic fibrosis and compromised liver function, underscoring the need to develop novel treatments for these conditions. Herein, our analyses of liver tissue samples from severe alcoholic hepatitis (SAH) patients and two murine models of ALD reveals that the ALD phenotype was associated with upregulation of the transcription factor ETS domain-containing protein (ELK-3) and ELK-3 signaling activity coupled with downregulation of α/β hydrolase domain containing 10 (ABHD10) and upregulation of deactivating S-palmitoylation of the antioxidant protein Peroxiredoxin 5 (PRDX5). In vitro, we further demonstrate that ELK-3 can directly bind to the ABHD10 promoter to inhibit its transactivation. TGFβ1 and epidermal growth factor (EGF) signaling induce ABHD10 downregulation and PRDX5 S-palmitoylation via ELK-3. This ELK-3-mediated ABHD10 downregulation drives oxidative stress and disrupts mature hepatocyte function via enhancing S-palmitoylation of PRDX5’s Cys100 residue. In vivo, ectopic Abhd10 overexpression ameliorates liver damage in ALD model mice. Overall, these data suggest that the therapeutic targeting of the ABHD10-PRDX5 axis may represent a viable approach to treating ALD and other forms of hepatotoxicity.

Postpandemic rebound of adeno‐associated virus type 2 (AAV2) infections temporally associated with an outbreak of unexplained severe acute hepatitis in children in the United Kingdom

AbstractOver 1000 cases of unexplained severe acute hepatitis in children have been reported to date worldwide. An association with adeno‐associated virus type 2 (AAV2) infection, a human parvovirus, prompted us to investigate the epidemiology of AAV in the United Kingdom. Three hundred pediatric respiratory samples collected before (April 03, 2009–April 03, 2013) and during (April 03, 2022) the COVID‐19 pandemic were obtained. Wastewater samples were collected from 50 locations in London (August 2021–March 2022). Samples were tested for AAV using real‐time polymerase chain reaction followed by sequencing. Selected adenovirus (AdV)‐positive samples were also sequenced. The detection frequency of AAV2 was a sevenfold higher in 2022 samples compared with 2009–2013 samples (10% vs. 1.4%) and highest in AdV‐positive samples compared with negatives (10/37, 27% vs. 5/94, 5.3%, respectively). AAV2‐positive samples displayed high genetic diversity. AAV2 sequences were either very low or absent in wastewater collected in 2021 but increased in January 2022 and peaked in March 2022. AAV2 was detected in children in association with AdV of species C, with a highest frequency in 2022. Our findings are consistent with the expansion of the population of children unexposed to AAV2, leading to greater spread of the virus once distancing restrictions were lifted.

Acute severe hepatitis of unknown origin in children in Canada.

In spring 2022, a series of reports from the United Kingdom and the United States identified an increase in the incidence of acute severe hepatitis in children. The Public Health Agency of Canada (PHAC) collaborated with provincial/territorial health partners to investigate in Canada. Clinical hepatitis, or inflammation of the liver, is not reportable in Canada, so to determine if an increase was occurring above historical levels, the baseline incidence in Canada was estimated. This article estimates the pre-existing baseline incidence of acute severe hepatitis of unknown origin in children in Canada using administrative databases. It further summarizes the outbreak investigation using information from the national case report forms. A committee with representatives from PHAC and provincial/territorial health partners was established to investigate current cases in Canada. A national probable case definition and case report form were developed, and intentionally created to be highly sensitive to capture all potential cases for etiological investigations. To estimate a nationally representative baseline incidence, hospitalization data were extracted from the Discharge Abstract Database and was combined with data from Québec from the Ministère de la Santé et des Services sociaux. Twenty-eight probable cases of acute severe hepatitis of unknown origin in children were reported between October 1, 2021, to September 23, 2022, by six provinces: British Columbia=1; Alberta=5; Saskatchewan=1; Manitoba=3; Ontario=14; and Québec=4. The estimated national baseline incidence was an average of 70 cases annually, or 5.8 cases per month. There was no apparent increase above the estimated historical baseline levels.

Investigation of acute severe hepatitis in children: A review of liver transplant data, Canada, 2021-2022.

An increase in severe acute hepatitis of unknown etiology was first reported in the United Kingdom in April 2022. Following this report, the Public Health Agency of Canada connected with three paediatric liver transplant centres across Canada to determine if an increase in liver transplants was noted. Data demonstrated no observable increase in the number of transplants conducted in 2022. These data in conjunction with a federal, provincial, territorial investigation provided insight into the situation in Canada.

Management of the acute on chronic liver failure in the intensive care unit.

Acute on chronic liver failure (ACLF) reflects the development of organ failure(s) in a patient with cirrhosis and is associated with high short-term mortality. Given that ACLF has many different 'phenotypes', medical management needs to take into account the relationship between precipitating insult, organ systems involved and underlying physiology of chronic liver disease/cirrhosis. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection, severe alcoholic hepatitis and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery. Management of these patients is complex since they are prone to develop new organ failures and infectious or bleeding complications. ICU therapy parallels that applied in the general ICU population in some complications but differs in others. Given that liver transplantation in ACLF is an emerging and evolving field, multidisciplinary teams with expertise in critical care and transplant medicine best accomplish management of the critically ill ACLF patient. The focus of this review is to identify the common complications of ACLF and to describe the proper management in critically ill patients awaiting liver transplantation in our centres, including organ support, prognostic assessment and how to assess when recovery is unlikely.

Clinicopathologic Features of Severe Acute Hepatitis Associated With Adenovirus Infection in Children.

A recent increase in reports of severe acute hepatitis of unknown etiology in children is under investigation. Although adenovirus has been frequently detected, its role remains unclear, and systematic histopathologic analysis is lacking. We conducted a retrospective study of 11 children hospitalized between October 2021 and May 2022 with unexplained acute hepatitis and concurrent adenovirus infection. Liver biopsies collected shortly after admission demonstrated moderately to severely active hepatitis in 8/11 (73%) cases, characterized by marked portal mixed inflammation, moderate-to-severe interface activity, and milder lobular inflammation. Clusters of plasma cells were present in 6/11 (55%) cases, mimicking autoimmune hepatitis. Semiquantitative scoring of 17 discrete histologic features found that greater degrees of portal inflammation, interface activity, bile duct injury, bile ductular reaction, lobular inflammation, Kupffer cell activation, and hepatocyte focal necrosis were significantly more common in these cases in comparison to the control group of unexplained acute severe hepatitis without adenovirus infection. Liver biopsy immunohistochemistry was negative for adenovirus in all cases. Polymerase chain reaction testing of liver tissue was positive for the enteric adenovirus serotypes 41 (species F) in 10/11 (91%) cases. An immunoprofile study of hepatic infiltrating lymphocytes in 1 patient revealed the presence of large numbers of CD3 + and CD4 + lymphocytes. Nine patients received supportive treatment without steroids and recovered without the need for liver transplantation. In summary, liver injury in children with severe acute hepatitis and adenovirus infection is characterized by a hepatitic pattern that resembles severe autoimmune hepatitis and may represent an immune-mediated process associated with viral infection.

Orchestrated regulation of immune inflammation with cell therapy in pediatric acute liver injury.

Acute liver injury (ALI) in children, which commonly leads to acute liver failure (ALF) with the need for liver transplantation, is a devastating life-threatening condition. As the orchestrated regulation of immune hemostasis in the liver is essential for resolving excess inflammation and promoting liver repair in a timely manner, in this study we focused on the immune inflammation and regulation with the functional involvement of both innate and adaptive immune cells in acute liver injury progression. In the context of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, it was also important to incorporate insights from the immunological perspective for the hepatic involvement with SARS-CoV-2 infection, as well as the acute severe hepatitis of unknown origin in children since it was first reported in March 2022. Furthermore, molecular crosstalk between immune cells concerning the roles of damage-associated molecular patterns (DAMPs) in triggering immune responses through different signaling pathways plays an essential role in the process of liver injury. In addition, we also focused on DAMPs such as high mobility group box 1 (HMGB1) and cold-inducible RNA-binding protein (CIRP), as well as on macrophage mitochondrial DNA-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in liver injury. Our review also highlighted novel therapeutic approaches targeting molecular and cellular crosstalk and cell-based therapy, providing a future outlook for the treatment of acute liver injury.

Efficacy of Fecal Microbiota Transplant in the Treatment of Severe Alcoholic Hepatitis Compared to Standard of Care in Humans: A Systematic Review

Severe alcoholic hepatitis (SAH) is a life-threatening condition with limited treatment options. Fecal microbiota transplant (FMT) has emerged as a potential therapeutic approach, targeting the imbalance in the gut microbiota observed in SAH patients. This review aims to assess the efficacy of FMT in improving outcomes and compare it with the standard of care in SAH. A systematic review of five multi-patient studies conducted in India was performed. Out of these studies, four were conducted as clinical trials, whereas one was a retrospective observational study design. The primary outcome assessed was survival rates at various time points, including day 28, day 90, and one year. Secondary outcomes included the resolution of complications such as hepatic encephalopathy, ascites, and infections.&#x0D; Analysis of the studies revealed a significant improvement in survival rates among SAH patients who underwent FMT compared to the standard of care. FMT also demonstrated a reduction in the incidence of complications, including hepatic encephalopathy, ascites, and infections. Additionally, FMT has been associated with positive changes in gut microbiota diversity and a decrease in the colonization of pathogenic taxa. However, the review identified several limitations, including the small sample sizes and the lack of randomized controlled trials. Further research, including conducting larger clinical trials, is necessary to strengthen the evidence for the efficacy of FMT in treating SAH. Additionally, future studies should explore the long-term effects of FMT, its impact on inflammatory cytokine levels, and the potential for personalized approaches based on individual gut microbiota profiles.&#x0D; In conclusion, this review provides evidence supporting the potential benefits of FMT in the management of severe alcoholic hepatitis. FMT represents a promising alternative to the standard of care and holds promise as a cost-effective treatment modality for eligible SAH patients. Future research should address the identified limitations and explore the optimal implementation of FMT in clinical practice.

Current and future treatment for alcoholic-related liver diseases.

The socioeconomic burden of alcohol-related liver disease has been increasing worldwide. Its prevalence is underestimated, and patients with alcohol-related liver disease are rarely diagnosed in the earlier phase of the disease spectrum. Alcoholic hepatitis is a distinct syndrome with life-threatening signs of systemic inflammation. In severe alcoholic hepatitis, prednisolone is indicated as the first-line treatment even with the possibility of various complications. Early liver transplantation can be another option for highly selected patients with a null response to prednisolone. Most importantly, abstinence is the mainstay of long-term care, but relapse is frequent among patients. Recent findings on the pathogenesis of alcoholic hepatitis have enabled us to discover new therapeutic targets. Preventing hepatic inflammation, reducing oxidative stress, improving gut dysbiosis, and enhancing liver regeneration are the main targets of emerging therapies. Herein, we review the pathogenesis, current treatment, and barriers to successful clinical trials of alcoholic hepatitis. Additionally, clinical trials for alcoholic hepatitis, either ongoing or recently completed, will be briefly introduced.