Complementary and alternative medicines and liver disease.

Complementary and alternative medicines (CAM) include conventional medical treatments. Patients worldwide use CAM at alarming rates; thus, reports of CAM-related DILI have been on the rise. The clinical presentations include asymptomatic liver test abnormalities, acute hepatitis with or without jaundice, acute cholestatic liver disease (bland or with hepatitis), acute liver failure, severe hepatitis with features of portal hypertension, and acute decompensation of known or unknown cirrhosis that can lead to acute-on-chronic liver failure. Acute hepatitis with or without necrosis, hepatocellular and canalicular cholestasis, herb-induced or CAM-triggered autoimmune hepatitis, granulomatous hepatitis, severe steatohepatitis, and vanishing bile duct syndrome are common liver biopsy findings in CAM-DILI. The presence of preexisting liver disease predicts severe liver injury, risk of progression to liver failure, and decreased transplant-free survival in patients with CAM-DILI. This review discusses global epidemiology and trends in CAM-DILI, clinical presentation, assessment and outcomes, commonly emerging threats in the context of hepatotoxic herbs, pragmatic assessment of "liver beneficial" herbs and health care myths, patient communication, regulatory framework, and future directions on research in CAM.

Clinical outcomes related to portal pressures before and after embolization of large portosystemic shunts in cirrhosis.

Objectives: Embolization of large portosystemic shunts effectively controls gastric variceal bleeding and prevents hepatic encephalopathy. The significance of dynamic changes in hepatic venous pressure gradient before and after embolization on clinical events and patient outcomes remains unknown. Methods: In this retrospective single-center series, 46 patients with gastric variceal bleeding, hepatic encephalopathy, or both undergoing embolization (January 2018 to October 2020) were included, and dynamic changes in portal pressures were analyzed against patient outcomes. Results: Males predominated. The most common portosystemic shunt syndrome was the lienorenal shunt. In all, 34 patients underwent embolization for hepatic encephalopathy and 11 for gastric variceal bleeding. The proportion of patients surviving at the end of 12 and 32 months was 86.96 and 54.35%, respectively. The hepatic venous pressure gradient before shunt embolization was 13.4 ± 3.2 and 16.9 ± 3.7 mm Hg after occlusion (p < 0.001). Bleeding from varices on overall follow-up was notable in five patients (10.9%), and overt hepatic encephalopathy in four (N = 42, 9.5%) patients at 6-12 months. The development of infections within 100 days and beyond the first year was associated with the risk of dying at the end of 12 and 32 months, respectively. Elevation of hepatic venous pressure gradient by >4 mm Hg from baseline and an absolute increase to >16 mm Hg immediately post-procedure significantly predicted the development of early- and late-onset ascites, respectively. Conclusion: Close monitoring for the development of infections and optimization of beta-blockers and diuretics after shunt embolization may improve clinical outcomes and help identify patients who will benefit from liver transplantation pending prospective validation.

Ashwagandha-induced liver injury-A case series from India and literature review.

BACKGROUND: Ashwagandha herb is commonly used in Ayurveda and a "fad" dietary supplement for a host of indications based on low levels of evidence. Recently, ashwagandha was implicated in multiple reports of herb-induced liver injury (HILI), mainly from the United States. We present the first, and currently largest, series of ashwagandha-HILI from multiple centers in India. METHODS: We retrospectively analyzed the respective institutional electronic medical records for ashwagandha-HILI. Patients consuming ashwagandha as part of multiherbal formulations or along with other known hepatotoxic supplements or medicines were excluded. All patients underwent a detailed diagnostic workup to exclude competing causes reasonably. Where possible, the implicated herbal formulation was retrieved and subjected to chemical analysis. RESULTS: Out of 23 patients with liver injury from ashwagandha (January 2019 to December 2022), we report 8 patients with single-ingredient formulation-related HILI. Study cohort was male predominant, and cholestatic hepatitis was the commonest presentation. Five patients had underlying chronic liver disease; 3 presented with acute-on-chronic liver failure, and all 3 died on follow-up. In others, the liver injury was prolonged, nonetheless self-limiting. Liver biopsy revealed cholestatic features predominantly with hepatocellular necrosis and lymphocyte/eosinophil predominant portal-based inflammation. One patient progressed to chronic HILI. Chemical analysis revealed only natural phytochemicals without adulteration or contamination. CONCLUSIONS: Ashwagandha-HILI presents with cholestatic hepatitis and can lead to the syndrome of acute-on-chronic liver failure with high mortality in those with pre-existing liver disease. Educating the public on avoiding the use of potentially toxic and unrecommended herbal supplements can help mitigate the avoidable liver disease burden in the community.

Significant gut microbiota related to patterns of drinking and alcohol relapse in patients with alcoholic hepatitis undergoing stool transplant or corticosteroid therapy.

Alcohol-induced gut microbiota (GM) alterations are linked to alcohol use disorder (AUD) pathogenesis. Healthy donor stool transplant (fecal microbiota transplant [FMT]) reduced alcohol desire and improved clinical outcomes in small animal and human studies. Baseline and post-therapy-related GM changes in a real-world cohort with severe alcohol-related liver disease and AUD, patterns of drinking, and relapse have not been studied. We prospectively analyzed retrospective clinical data and stored samples to examine GM alterations in a cohort of severe alcohol-associated hepatitis (SAH) patients who underwent FMT or corticosteroid treatment followed for at least 12 months. The GM changes at baseline in the context of a pattern of drinking (binge vs. every day) and baseline and post-treatment alcohol relapse status (relapser vs. non-relapser). We identified 28 patients on FMT and 25 on corticosteroids who survived 1 year post-treatment. After necessary exclusions, the final cohort for various grouped GM analysis included 16 patients in the FMT arm and 14 on corticosteroids. Pedobacter and Streptophyta species at the commencement of treatment predicted alcohol relapse in steroid-ineligible patients receiving FMT and steroid-treated patients, respectively. At 6-12 months post-FMT, non-relapsers had elevated short-chain fatty acid-producing bacterial taxa linked with lower alcohol cravings. Alcohol relapse was significantly more in those on steroid therapy and was associated with the upregulation of the nucleotide metabolism pathway related to ethanol metabolism. We demonstrate pertinent baseline and post-treatment intestinal bacterial alterations that impact patterns of AUD patterns and relapse in SAH patients in the context of the therapy offered.

Multi-center prospective survey of hepatocellular carcinoma in Kerala: More than 1,200 cases.

BACKGROUND: Hepatocellular carcinoma (HCC) is considered uncommon in India. The aim of this study was to document the demographic characteristics and clinical aspects of HCC in Kerala, India. METHODS: A survey of HCC in Kerala was performed. All gastroenterologists in the region were invited. From May 2018 to April 2020, data was collected in a standardized questionnaire. RESULTS: Forty-three doctors from 15 centers contributed the data. Total 1217 patients were analyzed. This is the largest state-wide survey of HCC in India. HCC was more common in men (90%) than in women (p < 0.01). The etiology of liver disease was hepatitis B virus (7%), hepatitis C virus (4%) and alcohol (40%). Diabetes mellitus was present in 64%, hypercholesterolemia in 17% and hypertension in 38%. Obesity was present in 33% and 15% were overweight. Non-alcoholic fatty liver disease (NAFLD) with or without metabolic syndrome was present in 44%. Serum alpha-fetoprotein was > 400 ng/mL in 24%, total tumor diameter was > 5 cm in 59%, portal vein invasion was seen in 35% and distant metastasis was seen in 15%. Specific therapy was given to 52%. Treatments given included liver transplantation (n = 24), liver resection (n = 39) and transarterial chemoembolization (TACE, n = 184). Although the study was not designed to compare survival, patients who had liver transplantation had longer survival (median 69 months) compared to matched patients given only TACE (median 18 months) (p = 0.03). CONCLUSION: HCC is common in Kerala, India. NAFLD has a predominant association with HCC in Kerala. Most of the patients report late when curative treatment is not possible.

Investigating the correlation between COVID-19 and the progression of chronic liver disease.

INTRODUCTION: The novel coronavirus disease 2019 has thrown light on various heterogeneous afflictions of newly emerging viruses on the human body. Early reports demonstrated direct effect of novel coronavirus on the liver, but subsequently, this did not stand up to validation. The SARS-CoV-2 virus affects the liver differentially; in healthy compared to those with preexisting liver disease. AREAS COVERED: This exhaustive paper reviews the current, literature on mechanisms by which COVID-19 affects the healthy liver and those with preexisting liver disease such as alcohol-related and nonalcoholic fatty liver, autoimmune liver disease, chronic liver disease and cirrhosis, hepatocellular carcinoma, viral hepatitis, and liver transplant recipients, with special mention on drug-and herb-induced liver injury with COVID-19 therapies. Search methodology: the review (Dec. 2022 - Jan. 2023) is based on PubMed (NLM) search using the keyword 'COVID' with supplementary searches using 'fibrosis;' 'liver;' 'cirrhosis;' 'CLD;' 'NAFLD;' 'NASH;' 'hepatocellular carcinoma;' 'hepatitis;' 'fatty liver;' 'alcohol;' 'viral;' 'transplant;' and 'liver failure.' EXPERT OPINION: Direct liver tropism of SARS-CoV-2 does not cause liver damage. Adverse events following infection depend on the severity of liver disease, the severity of COVID-19, and other risk factors such as metabolic syndrome and older age. Alcohol-related liver disease independently predicts adverse outcomes.

Clinical outcomes associated with complementary and alternative medicine-related "immunity-boosting" practices in patients with cirrhosis during the COVID-19 pandemic - an observational study.

During the coronavirus disease 2019 pandemic, Ayurvedic herbal supplements and homeopathic immune boosters (IBs) were promoted as disease-preventive agents. The present study examined the clinical outcomes among patients with chronic liver disease who presented with complications of portal hypertension or liver dysfunction temporally associated with the use of IBs in the absence of other competing causes. This single-center retrospective observational cohort study included patients with chronic liver disease admitted for the evaluation and management of jaundice, ascites, or hepatic encephalopathy temporally associated with the consumption of IBs and followed up for 180 days. Chemical analysis was performed on the retrieved IBs. From April 2020 to May 2021, 1022 patients with cirrhosis were screened, and 178 (19.8%) were found to have consumed complementary and alternative medicines. Nineteen patients with cirrhosis (10.7%), jaundice, ascites, hepatic encephalopathy, or their combination related to IBs use were included. The patients were predominantly male (89.5%). At admission, 14 (73.75%) patients had jaundice, 9 (47.4%) had ascites, 2 (10.5%) presented with acute kidney injury, and 1 (5.3%) had overt encephalopathy. Eight patients (42.1%) died at the end of the follow up period. Hepatic necrosis and portal-based neutrophilic inflammation were the predominant features of liver biopsies. IB analysis revealed detectable levels of (heavy metals) As (40%), Pb (60%), Hg (60%), and various hepatotoxic phytochemicals. Ayurvedic and Homeopathic supplements sold as IBs potentially cause the worsening of preexisting liver disease. Responsible dissemination of scientifically validated, evidence-based medical health information from regulatory bodies and media may help ameliorate this modifiable liver health burden.

A series of homeopathic remedies-related severe drug-induced liver injury from South India.

INTRODUCTION: Homeopathic remedies are highly diluted formulations without proven clinical benefits, traditionally believed not to cause adverse events. Nonetheless, published literature reveals severe local and non-liver-related systemic side effects. We present the first series on homeopathy-related severe drug-induced liver injury (DILI) from a single center. METHODS: A retrospective review of records from January 2019 to February 2022 identified 9 patients with liver injury attributed to homeopathic formulations. Competing causes were comprehensively excluded. Chemical analysis was performed on retrieved formulations using triple quadrupole gas chromatography-mass spectrometry and inductively coupled plasma atomic emission spectroscopy. RESULTS: Males predominated with a median age of 54 years. The most typical clinical presentation was acute hepatitis, followed by acute on chronic liver failure. All patients developed jaundice, and ascites were notable in one-third of the patients. Five patients had underlying chronic liver disease. COVID-19 prevention was the most common indication for homeopathic use. Probable DILI was seen in 77.8%, and hepatocellular injury predominated (66.7%). Four (44.4%) patients died (3 with chronic liver disease) at a median follow-up of 194 days. Liver histopathology showed necrosis, portal and lobular neutrophilic inflammation, and eosinophilic infiltration with cholestasis. A total of 29 remedies were consumed between 9 patients, and 15 formulations were analyzed. Toxicology revealed industrial solvents, corticosteroids, antibiotics, sedatives, synthetic opioids, heavy metals, and toxic phyto-compounds, even in 'supposed' ultra-dilute formulations. CONCLUSION: Homeopathic remedies potentially result in severe liver injury, leading to death in those with underlying liver disease. The use of mother tinctures, insufficient dilution, poor manufacturing practices, adulteration and contamination, and the presence of direct hepatotoxic herbals were the reasons for toxicity. Physicians, the public, and patients must realize that Homeopathic drugs are not 'gentle placebos.'

Identification and Analysis of Gut Microbiota and Functional Metabolism in Decompensated Cirrhosis with Infection.

Background and Aims: Intestinal dysbiosis play a role in the adverse outcomes of sepsis and septic shock. However, variations in bacterial diversity and microbiota-related functional metabolic alterations within the gut microbiome in decompensated cirrhosis (DC) patients with infection remain unknown. Methods: We conducted 16-srRNA sequencing on stool samples (n=51: sepsis, 27/no sepsis, 24) collected from consecutive DC patients upon admission. Bacterial diversity, significant taxa, and respective metabolic profiling were performed based on subgroup comparisons. Conet/Cytoscape was utilized to identify significant non-random patterns of bacterial copresence and mutual exclusion for clinical events. Results: Genera associated with pathogenicity in conditions of immune exhaustion (Corynebacterium, Lautropia) were predominant in patients with sepsis. Metabolic pathways associated with oxidative stress and endotoxemia [lipopolysaccharide (LPS) synthesis and sulfur relay] were significantly upregulated in sepsis. Specific taxa were associated with sites of infection in DC patients. Protective oxidant pathways that increase glutathione were upregulated in those without sepsis. Gammaproteobacteria family of sulfur-metabolizing bacteria, exaggeration of orally predominant pathogens (Prevotella), and pathways of severe LPS-related hyperinflammatory stress were notable in those with interleukin-6 levels >1,000 pg/dL. Pathogenic genera related to an immune deficient state was significant in DC with ≥2 infection episodes. Megamonas was associated with survival during the same admission. Conclusions: Specific gut microbiota and their metabolites were associated with sepsis and related events in patients with DC. Identifying beneficial strains that reduce immune exhaustion and supplementation of favorable metabolites could improve therapeutics for DC and sepsis, for which larger prospective, well controlled population-based studies remain an unmet need.

Clinical outcomes and gut microbiota analysis of severe alcohol-associated hepatitis patients undergoing healthy donor fecal transplant or pentoxifylline therapy: single-center experience from Kerala.

Background: Severe alcohol-associated hepatitis (SAH) patients with infections have a high short-term mortality rate. Gut microbiota dysbiosis plays an important role in the pathogenesis of SAH. Preliminary studies have demonstrated long-term benefits with healthy donor fecal microbiota transplantation (FMT). Data on FMT compared with pentoxifylline for SAH and relevant gut microbial changes are lacking in literature. Methods: From January 2019 to February 2021, retrospective analysis of a single hospital's records revealed 47 SAH patients undergoing FMT (100 mL/day via nasoduodenal tube for 7 days) and 25 matched patients receiving pentoxifylline (400 mg/8 h for 28 days). The primary end point was a 6-month survival rate. Secondary end points included incidence of ascites, hepatic encephalopathy, infections, acute kidney injury, and gut microbiota changes between post-therapy groups. Biomarker discovery and network analysis were also performed to identify significant taxa of gut microbiota in post-treatment groups in retrospectively stored stool samples. Results: All were males. The 6-month survival rate was higher in the patients undergoing FMT than in patients receiving pentoxifylline (83.0% vs 56.0%, P = 0.012). At the end of 6-month follow-up, the incidences of clinically significant ascites (56.0% vs 25.5%, P = 0.011), hepatic encephalopathy (40.0% vs 10.6%, P = 0.003), and critical infections (52.0% vs 14.9%, P < 0.001) in patients administered pentoxifylline were significantly higher than those in patients treated with FMT. At 3 months, biomarker analysis revealed a significant abundance of Bifidobacterium and Eggerthella in the FMT group and the pentoxifylline group, respectively. At 6 months, Bifidobacterium in the FMT group and pathogenic Aerococcaceae in the pentoxifylline group were notable. Network analysis showed beneficial taxa (Bifidobacterium) as a central influencer in those undergoing FMT at 6 months. Conclusions: Healthy donor FMT improved survival rate and reduced liver-related complications compared with pentoxifylline. These clinical benefits were associated with favorable modulation of intestinal bacterial communities. Difficult-to-treat SAH patients may be safely bridged to transplantation using FMT. Controlled trials evaluating long-term outcomes are an unmet need.

Spectrum of drug-induced liver injury in a tertiary hospital in southern India.

Background Anti-tuberculosis drugs are thought to account for about 50% of drugs that cause liver injury in India. We show that the spectrum of drugs is much wider than previously reported. Methods We evaluated all patients with unexplained acute liver injury presenting during 2006-2016 using a structured proforma for drug-induced liver injury (DILI). The Roussel Uclaf Causality Assessment Method was used to assess causality. Results DILI was found in 143 of 2534 patients with acute liver injury. Nineteen patients had probable ayurvedic DILI. The other common causes of DILI were statins (16 patients) and anti-tuberculosis drugs (11 patients). Eight patients had DILI post-liver transplant. Fluconazole was the most common cause of post-liver transplant DILI. Chronic DILI (abnormal liver function test after 12 months of stopping the suspected drug) was found in 2 patients. Conclusion In otherwise unexplained acute liver injury, DILI due to ayurvedic drugs should be sought. DILI should be considered in post-liver transplant patients. Patients with DILI should be monitored for at least 12 months to exclude progression to chronic DILI.

Ayurvedic treatment induced severe alcoholic hepatitis and non-cirrhotic portal hypertension in a 14-year-old girl.

We report a novel and as yet undescribed clinical scenario in a young girl with liver failure, in whom, the liver histopathology was suggestive of alcoholic hepatitis in the background of hepatoportal sclerosis and incomplete septal cirrhosis. An extensive clinical and investigational evaluation revealed chronic consumption of multiple Ayurvedic herbal medications for seizure disease. Six months after stopping herbal medicines, the repeat liver biopsy demonstrated resolution of alcohol-related changes but persistence of classical features of non-cirrhotic portal hypertension. Analysis of the retrieved agents, including state of the art chemical and toxicology analysis, using gas chromatography and mass spectroscopy methods demonstrated multiple organic and inorganic toxins associated with acute alcohol and arsenic poisoning related hepatoportal sclerosis/incomplete septal cirrhosis in the young girl.

Long-term Outcomes of Stool Transplant in Alcohol-associated Hepatitis-Analysis of Clinical Outcomes, Relapse, Gut Microbiota and Comparisons with Standard Care.

Background: Healthy donor fecal microbiota transplantation (FMT) was preliminarily shown to have clinical benefits in hepatic encephalopathy (HE), severe alcohol-associated hepatitis (SAH), and alcohol use disorder. However, the long-term outcomes of FMT and the gut microbiota (GM) changes in patients with SAH are unknown. Methods: Patients with SAH who underwent FMT (N = 35) or standard of care (SoC, N = 26) from May 2017 to June 2018 were included, and their stored stool samples were analyzed prospectively. Clinical outcomes, including infections, hospitalizations, critical illness, alcohol relapse, and survival, were evaluated. Metagenomic analysis was undertaken to identify the relative abundances (Ras) and significant taxa at baseline and post-therapy (up to three years) among survivors between the two groups. Results: At follow-up, the incidences of ascites, HE, infections, and major hospitalizations were significantly higher in the SoC than in the FMT group (P < 0.05). Alcohol relapse was lower (28.6% versus 53.8%), and the time to relapse was higher in the FMT than in the SoC group (P = 0.04). Three-year survival was higher in the FMT than in the SoC group (65.7% versus 38.5%, P = 0.052). Death due to sepsis was significantly higher in the SoC group (N = 13/16, 81.2%; P = 0.008). GM analysis showed a significant increase in the RA of Bifidobacterium and a reduction in the RA of Acinetobacter in the FMT group. Beyond one to two years, the RA of Porphyromonas was significantly higher and that of Bifidobacterium was lower in the SoC than in the FMT group. Conclusions: In terms of treatment for patients with SAH, healthy donor FMT is associated with significantly lesser ascites, infections, encephalopathy, and alcohol relapse (with a trend toward higher survival rates) than SoC, associated with beneficial GM modulation. Larger controlled studies on FMT are an unmet need.

Gut Barrier and Microbiota in Cirrhosis.

Gut microbiota and their homeostatic functions are central to the maintenance of the intestinal mucosal barrier. The gut barrier functions as a structural, biological, and immunological barrier, preventing local and systemic invasion and inflammation of pathogenic taxa, resulting in the propagation or causation of organ-specific (liver disease) or systemic diseases (sepsis) in the host. In health, commensal bacteria are involved in regulating pathogenic bacteria, sinister bacterial products, and antigens; and help control and kill pathogenic organisms by secreting antimicrobial metabolites. Gut microbiota also participates in the extraction, synthesis, and absorption of nutrient metabolites, maintains intestinal epithelial integrity and regulates the development, homeostasis, and function of innate and adaptive immune cells. Cirrhosis is associated with local and systemic immune, vascular, and inflammatory changes directly or indirectly linked to perturbations in quality and quantity of intestinal microbiota and intestinal mucosal integrity. Dysbiosis and gut barrier dysfunction are directly involved in the pathogenesis of compensated cirrhosis and the type and severity of complications in decompensated cirrhosis, such as bacterial infections, encephalopathy, extrahepatic organ failure, and progression to acute on chronic liver failure. This paper reviews the normal gut barrier, gut barrier dysfunction, and dysbiosis-associated clinical events in patients with cirrhosis. The role of dietary interventions, antibiotics, prebiotics, probiotics, synbiotics, and healthy donor fecal microbiota transplantation (FMT) to modulate the gut microbiota for improving patient outcomes is further discussed.

The role of gut microbiota in clinical complications, disease severity, and treatment response in severe alcoholic hepatitis.

BACKGROUND: Dysbiotic gut bacteria engage in the development and progression of severe alcoholic hepatitis (SAH). We aimed to characterize bacterial communities associated with clinical events (CE), identify significant bacteria linked to CE, and define bacterial relationships associated with specific CE and outcomes at baseline and after treatment in SAH. METHODS: We performed 16-s rRNA sequencing on stool samples (n=38) collected at admission and the last follow-up within 90 days in SAH patients (n=26; 12 corticosteroids; 14 granulocyte colony-stimulating factor, [G-CSF]). Validated pipelines were used to plot bacterial communities, profile functional metabolism, and identify significant taxa and functional metabolites. Conet/NetworkX® was utilized to identify significant non-random patterns of bacterial co-presence and mutual exclusion for clinical events. RESULTS: All the patients were males with median discriminant function (DF) 64, Child-Turcotte-Pugh (CTP) 12, and model for end-stage liver disease (MELD) score 25.5. At admission, 27%, 42%, and 58% had acute kidney injury (AKI), hepatic encephalopathy (HE), and infections respectively; 38.5% died at end of follow-up. Specific bacterial families were associated with HE, sepsis, disease severity, and death. Lachnobacterium and Catenibacterium were associated with HE, and Pediococcus with death after steroid treatment. Change from Enterococcus (promotes AH) to Barnesiella (inhibits E. faecium) was significant after G-CSF. Phenylpropanoid-biosynthesis (innate-immunity) and glycerophospholipid-metabolism (cellular-integrity) pathways in those without infections and the death, respectively, were upregulated. Mutual interactions between Enterococcus cecorum, Acinetobacter schindleri, and Mitsuokella correlated with admission AKI. CONCLUSIONS: Specific gut microbiota, their interactions, and metabolites are associated with complications of SAH and treatment outcomes. Microbiota-based precision medicine as adjuvant treatment may be a new therapeutic area.

Critical Update on the Diagnosis and Management of COVID-19 in Advanced Cirrhosis and Liver Transplant Recipients.

The novel coronavirus disease 2019 (COVID-19) pandemic has impacted health care worldwide, with specific patient populations, such as those with diabetes, cardiovascular disease, and chronic lung disease, at higher risk of infection and others at higher risk of disease progression. Patients with decompensated cirrhosis fall into the latter category and are a unique group that require specific treatment and management decisions because they can develop acute-on-chronic liver failure. In liver transplant recipients, the atypical immunity profile due to immunosuppression protects against downstream inflammatory responses triggered by COVID-19. This exhaustive review discusses the outcomes associated with COVID-19 in patients with advanced cirrhosis and in liver transplant recipients. We focus on the immunopathogenesis of COVID-19, its correlation with the pathogenesis of advanced liver disease, and the effect of immunosuppression in liver transplant recipients to provide insight into the outcomes of this unique patient population.

Critical Updates on Chronic Hepatitis B Virus Infection in 2021.

Chronic hepatitis B virus (HBV) infection is a global healthcare burden in the form of chronic liver disease, cirrhosis, liver failure and liver cancer. There is no definite cure for the virus and even though extensive vaccination programs have reduced the burden of liver disease in the future population, treatment options to eradicate the virus from the host are still lacking. In this review, we discuss in detail current updates on the structure and applied biology of the virus in the host, examine updates to current treatment and explore novel and state-of-the-art therapeutics in the pipeline for management of chronic HBV. Furthermore, we also specifically review clinical updates on HBV-related acute on chronic liver failure (ACLF). Current treatments for chronic HBV infection have seen important updates in the form of considerations for treating patients in the immune tolerant phase and some clarity on end points for treatment and decisions on finite therapy with nucleos(t)ide inhibitors. Ongoing cutting-edge research on HBV biology has helped us identify novel target areas in the life cycle of the virus for application of new therapeutics. Due to improvements in the area of genomics, the hope for therapeutic vaccines, vector-based treatments and focused management aimed at targeting host integration of the virus and thereby a total cure could become a reality in the near future. Newer clinical prognostic tools have improved our understanding of timing of specific treatment options for the catastrophic syndrome of ACLF secondary to reactivation of HBV. In this review, we discuss in detail pertinent updates regarding virus biology and novel therapeutic targets with special focus on the appraisal of prognostic scores and treatment options in HBV-related ACLF.

Hepatocellular Carcinoma in 2021: An Exhaustive Update.

Primary liver cancer is a challenging global health concern with an estimated more than a million persons to be affected annually by the year 2025. The commonest type is hepatocellular carcinoma (HCC), which has been increasing in incidence the world over, mostly due to chronic viral hepatitis B infection. In the last decade, paradigm changes in the etiology, understanding of molecular biology, and pathogenesis, including the role of gut microbiota; medical and surgical treatments, and outcome trends are notable. The application of omics-based technology has helped us unlock the molecular and immune landscape of HCC, through which novel targets for drug treatment such as immune-checkpoint inhibitors have been identified. Novel tools for the surveillance and diagnosis of HCC include protein-, genomics-, and composite algorithm-based clinical/biomarker panels. Magnetic resonance imaging-based novel techniques have improved HCC diagnosis through ancillary features that enhance classical criteria while positron emission tomography has shown value in prognostication. Identification of the role of gut microbiota in the causation and progression of HCC has opened areas for novel therapeutic research. A select group of patients still benefit from modified surgical and early interventional radiology treatments. Improvements in radiotherapy protocols, identification of parameters of futility among radiological interventions, and the emergence of novel first-line systemic therapies that include a combination of antiangiogenic and immune-checkpoint inhibitors have seen a paradigm change in progression-free and overall survival. The current review is aimed at providing exhaustive updates on the etiology, molecular biology, biomarker diagnosis, imaging, and recommended treatment options in patients with HCC.

Friend or Foe? Spontaneous Portosystemic Shunts in Cirrhosis-Current Understanding and Future Prospects.

Portal hypertension (PHT) in cirrhosis results from increased resistance to splanchnic blood flow secondary to parenchymal and vascular changes within the liver. In an attempt to counteract the increased portal pressure, two mechanisms simultaneously occur: splanchnic vasodilatation and formation of spontaneous portosystemic shunts (SPSS). Long considered to be a compensatory mechanism to decompress the portal venous system, it is now well established that SPSS are not only inefficient in decreasing the portal pressure but also contribute to reduced hepatocyte perfusion and increased splanchnic blood flow and resistance, associated with worsening PHT. Recent studies have described a high prevalence of SPSS in cirrhosis patients, increasing with liver dysfunction, and observed an association between the presence of SPSS and worse clinical outcomes. In cirrhosis patients with preserved liver functions, the presence of SPSS independently increases the risk of hepatic encephalopathy, variceal bleeding, and ascites, and reduces transplant-free survival. Moreover, the presence of SPSS in patients undergoing transjugular intrahepatic portosystemic shunting and liver transplant has been shown to variably affect the postprocedural outcome. This article provides an overview of the current understanding of the role of SPSS in the natural history of liver cirrhosis and their status as a therapeutic target and an imaging biomarker to identify patients at higher risk of developing complications of PHT.