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Efficacy and safety of anti-hepatic fibrosis drugs

World Journal of Gastroenterology 2020年第41期26卷 6304-6321页

作者： konstantinos damiris Zaid H Tafesh Nikolaos Pyrsopoulos Department of Medicine Rutgers-New Jersey Medical SchoolNewarkNJ 07103United States Medicine-Gastroenterology and Hepatology Rutgers-New Jersey Medical SchoolNewarkNJ 07103United States

Recent progress in our understanding of the pathways linked to progression from hepatic insult to cirrhosis has led to numerous novel therapies being investigated as potential cures and inhibitors of hepatic fibrogenesis. Liver cirrhosis is the final result of prolonged fibrosis, which is an intimate balance between fibrogenesis and fibrinolysis. A number of these complex mechanisms are shared across the various etiologies of liver disease. Thankfully, investigation has yielded some promising results in regard to reversal of fibrosis, particularly the indirect benefits associated with antiviral therapy for the treatment of hepatitis B and C and the farnesoid receptor agonist for the treatment of primary biliary cholangitis and metabolic associated fatty liver disease. A majority of current clinical research is focused on targeting metabolic associated fatty liver disease and its progression to metabolic steatohepatitis and ultimately cirrhosis, with some hope of potential standardized therapeutics in the near future. With our ever-evolving understanding of the underlying pathophysiology, these therapeutics focus on either controlling the primary disease(the initial trigger of fibrogenesis), interrupting receptor ligand interactions and other intracellular communications, inhibiting fibrogenesis, or even promoting resolution of fibrosis. It is imperative to thoroughly test these potential therapies with the rigorous standards of clinical therapeutic trials in order to ensure the highest standards of patient safety. In this article we will briefly review the key pathophysiological pathways that lead to liver fibrosis and present current clinical and experimental evidence that has shown reversibility of liver fibrosis and cirrhosis, while commenting on therapeutic safety.

关键词： Liver Fibrosis Cirrhosis Antifibrotic Pharmacotherapy Clinical trial Safety

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Hepatitis E in immunocompromised individuals

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World Journal of Hepatology 2022年第3期14卷 482-494页

作者： konstantinos damiris Mohamad Aghaie Meybodi Mumtaz Niazi Nikolaos Pyrsopoulos Department of Medicine Rutgers-New Jersey Medical SchoolNewarkNJ 07103United States Department of Medicine-Gastroenterology and Hepatology Rutgers-New Jersey Medical SchoolNewarkNJ 07103United States

Hepatitis E virus(HEV)originally identified as a cause of acute icteric hepatitis in developing countries has grown to be a cause of zoonotic viral hepatitis in developed countries such as the United *** there are eight identified genotypes to date,genotype 1(HEV1),HEV2,HEV3,HEV4 are the most common to infect ***1 and HEV2 are most common in developing countries including Latina America,Africa and Asia,and are commonly transmitted through contaminated water supplies leading to regional *** contrast HEV3 and HEV4 circulate freely in many mammalian animals and can lead to occasional transmission to humans through fecal contamination or consumption of undercooked *** incidence and prevalence of HEV in the United States is undetermined given the absence of FDA approved serological assays and the lack of commercially available *** majority of cases,HEV infection is a selflimiting hepatitis requiring only symptomatic ***,this is not the case in immunocompromised individuals,including those that have undergone solid organ or stem cell *** this subset of patients,chronic infection can be life threatening as hepatic insult can lead to inflammation and fibrosis with subsequent cirrhosis and *** need for re-transplantation as a result of post-transplant hepatitis is of great *** addition,there have been many reported incidents of extrahepatic manifestations,for which the exact mechanisms remain to be *** cornerstone of treatment in immunocompromised solid organ transplant recipients is reduction of immunosuppressive therapies,while attempting to minimize the risk of organ *** treatment options include ribavirin,and pegylated interferon alpha in those who have demonstrated ribavirin *** investigation assessing safety and efficacy of anti-viral therapy is imperative given the rising global health *** this concern,vaccination has been approved in Chin

关键词： Hepatitis E Hepatitis E virus Chronic hepatitis Acute hepatitis Immunocompromised Liver transplant

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Cellular based treatment modalities for unresectable hepatocellular carcinoma

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World Journal of Clinical Oncology 2021年第5期12卷 290-308页

作者： konstantinos damiris Hamza Abbad Nikolaos Pyrsopoulos Department of Medicine Rutgers New Jersey Medical SchoolNewarkNJ 07103United States Department of Medicine Division of Gastroenterology and HepatologyRutgers New Jersey Medical SchoolNewarkNJ 07103United States

Hepatocellular carcinoma(HCC)is the most common primary malignancy of the liver and is unfortunately associated with an overall poor prognosis and high *** and intermediate stages of HCC allow for treatment with surgical resection,ablation and even liver transplantation,however disease progression warrants conventional systemic *** years treatment options were limited to molecular-targeting medications,of which sorafenib remains the standard of *** recent development and success of immune checkpoint inhibitors has proven to be a breakthrough in the treatment of HCC,but there is an urgent need for the development of further novel therapeutic treatments that prolong overall survival and minimize *** investigation is focused on adoptive cell therapy including chimeric antigen receptor-T cells(CAR-T cells),T cell receptor(TCR)engineered T cells,dendritic cells,natural killer cells,and tumor infiltrating lymphocyte cells,which have shown remarkable success in the treatment of hematological and solid tumor *** this review we briefly introduce readers to the currently approved systemic treatment options and present clinical and experimental evidence of HCC immunotherapeutic treatments that will hopefully one day allow for revolutionary change in the treatment modalities used for unresectable *** also provide an up-to-date compilation of ongoing clinical trials investigating CAR-T cells,TCR engineered T cells,cancer vaccines and oncolytic viruses,while discussing strategies that can help overcome commonly faced challenges when utilizing cellular based treatments.

关键词： Hepatocellular carcinoma Immunotherapy Immune cells Adoptive T cell therapy Chimeric antigen receptor-T cell Clinical trials

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Nonalcoholic fatty liver disease is associated with worse intestinal complications in patients hospitalized for Clostridioides difficile infection

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World Journal of Hepatology 2021年第11期13卷 1777-1790页

作者： Yi Jiang Salil Chowdhury Bing-Hong Xu Mohamad Aghaie Meybodi konstantinos damiris Samanthika Devalaraju Nikolaos Pyrsopoulos Department of Medicine Rutgers New Jersey Medical SchoolNewarkNJ 07101United States Liver Center and Center for Asian Health RWJBH-Saint Barnabas Medical CenterFlorham ParkNJ 07932United States Department of Medicine Gastroenterology and HepatologyRutgers New Jersey Medical SchoolNewarkNJ 07101United States

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)has become the leading cause of chronic liver disease with increasing prevalence *** difficile infection(CDI)remains the most common cause of nosocomial diarrhea in developed *** To assess the impact of NAFLD on the outcomes of hospitalized patients with *** This study was a retrospective cohort *** Nationwide Inpatient Sample database was used to identify a total of 7239 adults admitted as inpatients with a primary diagnosis of CDI and coexisting NAFLD diagnosis from 2010 to 2014 using ICD-9 *** with CDI and coexisting NAFLD were compared to those with CDI and coexisting alcoholic liver disease(ALD)and viral liver disease(VLD),*** outcomes included mortality,length of stay,and total hospitalization *** outcomes were in-hospital *** regression was used for outcome analysis after adjusting for possible *** CDI with NAFLD was independently associated with lower rates of acute respiratory failure(2.7%vs 4.2%,P<0.01;2.7%vs 4.2%,P<0.05),shorter length of stay(days)(5.75±0.16 vs 6.77±0.15,P<0.001;5.75±0.16 vs 6.84±0.23,P<0.001),and lower hospitalization charges(dollars)(38150.34±1757.01 vs 46326.72±1809.82,P<0.001;38150.34±1757.01 vs 44641.74±1660.66,P<0.001)when compared to CDI with VLD and CDI with ALD,*** with NAFLD was associated with a lower rate of acute kidney injury(13.0%vs 17.2%,P<0.01),but a higher rate of intestinal perforation(P<0.01)when compared to VLD.A lower rate of mortality(0.8%vs 2.7%,P<0.05)but a higher rate of intestinal obstruction(4.6%vs 2.2%,P=0.001)was also observed when comparing CDI with NAFLD to *** Hospitalized CDI patients with NAFLD had more intestinal complications compared to CDI patients with VLD and *** microbiota dysbiosis may contribute to the pathogenesis of intestinal complications.

关键词： Nonalcoholic fatty liver disease Clostridioides difficile infection Gut microbiota Intestinal complications Alcoholic liver disease Viral liver disease

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