Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

An extended treatment protocol with pegylated interferon and ribavirin for hepatitis C recurrence after liver transplantation

AIM: To evaluate the efflicacy and tolerability of an extended treatment protocol and to determine the predictors of sustained virological response (SVR) after liver transplantation (LT).METHODS: Between August 2005 and November 2008, patients with recurrent hepatitis C virus (HCV) after LT were selected for treatment if liver biopsy showed at least grade 2 inflammation and/or stage 2 flibrosis. All patients were to receive pegylated interferon (PEG)/regimens combining ribavirin (RBV) for an additional 48 wk after HCV undetectability.RESULTS: Extended protocol treatment was initiated in thirty patients. Overall, 73% had end of treatmentresponse and 60% had SVR. Nineteen patients completed treatment per protocol, of them, sixteen (84%) had end of treatment response, and fourteen (74%) achieved SVR. Both early virological response and 24-week virological response were individually associated with SVR but this association was not signif icant on multivariate analysis. Eleven patients (37%) discontinued therapy due to adverse effects. Cytopenias were the most common and most severe adverse effect, and required frquent growth factor use, dose adjustments and treatment cessations. The risk of rejection was not increased.CONCLUSION: Recurrent HCV after LT can be safely treated with extended virological responseguided therpy using PEG/RBV, but requires close monitoring for treatment-related adverse effects, particularly cytopenias.

Association of non-alcoholic fatty liver disease and COVID-19: A literature review of current evidence

The coronavirus disease 2019(COVID-19)pandemic has swept through nations,crippled economies and caused millions of deaths worldwide.Many people diagnosed with COVID-19 infections are often found to develop liver injury,which,in a small portion of patients,progresses to severe liver disease.Liver injury in the form of elevated transaminases,hyperbilirubinemia and alterations in serum albumin has been observed to be higher in patients with severe forms of the disease.Those who already have insult to the liver from chronic disease,such as nonalcoholic fatty liver disease(NAFLD)may be at the greatest disadvantage.The severity of COVID-19 also seems to be driven by the presence of NAFLD and other co-morbidities.About 25%of the global population has NAFLD.With such a widespread prevalence of NAFLD,understanding the disease progression of COVID-19 and the occurrence of liver injury in this vulnerable population assumes great significance.In this review,we present an overview of COVID-19 infection in patients with NAFLD.

A Study on the Safety of Liver Biopsy Inpatients with Von Willebrand’s Disease

Objectives: Liver biopsy remains the gold standard for diagnosis of chronic liver diseases. Outpatient percutaneous biopsy is generally safe with a mortality rate of 0.17% and hospitalization rate for bleeding of 3%. Von Willebrand disease (vWD) syndrome is the most common inherited hematological disorder with a prevalence of 1% - 3% globally. We sought to study whether vWD increases the risk of bleeding for liver biopsies. Methods: All patients (n = 120) who underwent outpatient percutaneous liver biopsies from 1997 to 2007 were analyzed. Demographics, PT/INR, platelet count, vW antigen and ristocetin induced platelet aggregation were studied. Results: No vWD patients had major bleeding that required transfusion, hospitalization or surgery but 9 (75%) had minor local bleeding and all had ecchymosis, which resolved spontaneously within 24 hours. Conclusions: Patients with vW factor deficiency can undergo percutaneous liver biopsy without major bleeding. Minor bleeding may occur at a slightly higher rate. vWD is not a contraindication to percutaneous liver biopsy.

Mycophenolate mofetil for drug-induced vanishing bile duct syndrome

Amoxicillin/clavulanate is associated with liver injury, mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment, but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.

Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, how ever, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.

Recurrent hepatitis C after liver transplant

End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28 B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5 B polymerase inhibitors and NS5 A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients.

Liver injury in COVID-19:The hepatic aspect of the respiratory syndrome-what we know so far

The 2019 novel coronavirus disease(COVID-19)pandemic due to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has posed a serious threat to global public health.Although primarily,the infection causes lung injury,liver enzyme abnormalities have also been reported to occur during the course of the disease.We conducted an extensive literature review using the PubMed database on articles covering a broad range of issues related to COVID-19 and hepatic injury.The present review summarizes available information on the spectrum of liver involvement,the possible mechanisms and risk factors of liver injury due to SARS-CoV-2 infection,and the prognostic significance of the presence of liver injury.Hopefully,this review will enable clinicians,especially the hepatologists,to understand and manage the liver derangements they may encounter in these patients better and provide guidance for further studies on the liver injury of COVID-19.

Guillain-Barre syndrome associated with peginterferon alfa-2a for chronic hepatitis C: A case report

The recommended therapy for chronic hepatitis C (CHC) infection is the combination of a Pegylated interferon and Ribavirin. Almost all such patients on combination therapy experience one or more adverse events during the course of treatment. Significant neurological side effects are rare. A few cases of Bell's Palsy, chronic inflammatory demyelinating polyneuropathy and even one case of acute demyelinating polyneuropathy with atypical features for Guillain-Barre syndrome (GBS) associated with Interferon therapy have been reported but no report of GBS with typical features has been published. We present a case report of typical GBS associated with Peginterferon alfa-2a and Ribavirin used for treatment of CHC infection.

Hepatitis B infection among adults in the philippines:A national seroprevalence study

AIM:To determine the prevalence of hepatitis B surface antigen(HBsAg)seropositivity among adult Filipinos.METHODS:Testing for HBsAg was performed on serum samples from persons aged ≥ 20 years old who participated in the National Nutrition and Health Survey(NNHeS)conducted in 2003.Information on age,sex,marital status,educational attainment,employment status,and income were collected.For this study,marital status was classified as never married or otherwise(i.e.,married,divorced,separated,widowed);educational attainment was classified as high school graduate or below or at least some tertiary education;and employment status was classified as currently employed or currently unemployed.Annual income was divided into 4 quartiles in Philippine pesos(PhP):Q1,≤ PhP 53064;Q2,PhP 53065-92192;Q3,PhP 92193-173387;and Q4,≥ PhP 173388.Prevalence estimates were weighted so that they represented the general population.Social and demographic factors were correlated with HBsAg seropositivity.Multivariate analysis was used to determine independent predictors of HBsAg seropositivity.RESULTS:A total of 2150 randomly selected adults,20 years and over,out of the 4753 adult participants of NNHeS were tested for HBsAg.The HBsAg seroprevalence was 16.7%(95%CI:14.3%-19.1%),which corresponded to an estimated 7278968 persons infected with hepatitis B.There was no significant difference between males and females(17.5% vs 16.0%;P = 0.555).This corresponded to an estimated 3721775 men and 3557193 women infected with hepatitis B.The HBsAg seroprevalence peaked at age 20-39 years old,with declining prevalence in the older age groups.The only independent predictor of HBsAg seropositivity was the annual income,with persons in the highest income quartile being less likely to be HBsAg positive(age-adjusted OR = 0.51;95%CI:0.30-0.86)compared to subjects in the lowest income quartile.Sex,marital status,educational attainment,and employment status were not found to be independent predictors of HBsAg seropositivity.CONCLUSION:The high HBsAg seroprevalence among adults in the Philippines classifies the country as hyperendemic for HBV infection and appears unchanged over the last few decades.

Nonalcoholic Fatty Liver Disease(NAFLD)Name Change:Requiem or Reveille?

Nonalcoholic fatty liver disease(NAFLD)affects about a quarter of the world’s population and poses a major health and economic burden globally.Recently,there have been hasty attempts to rename NAFLD to metabolic-associated fatty liver disease(MAFLD)despite the fact that there is no scientific rationale for this.Quest for a“positive criterion”to diagnose the disease and destigmatizing the disease have been the main reasons put forth for the name change.A close scrutiny of the pathogenesis of NAFLD would make it clear that NAFLD is a heterogeneous disorder,involving different pathogenic mechanisms of which metabolic dysfunction-driven hepatic steatosis is only one.Replacing NAFLD with MAFLD would neither enhance the legitimacy of clinical practice and clinical trials,nor improve clinical care or move NAFLD research forward.Rather than changing the nomenclature without a strong scientific backing to support such a change,efforts should be directed at understanding NAFLD pathogenesis across diverse populations and ethnicities which could potentially help develop newer therapeutic options.

Nonalcoholic Fatty Liver Disease after Liver Transplant

Nonalcoholic fatty liver disease(NAFLD)is one of the most common causes of chronic liver disease in the world.The rising prevalence of nonalcoholic steatohepatitis(NASH)has led to a 170%increase in NASH cirrhosis as the listing indication for liver transplantation from 2004 to 2013.As of 2018,NASH has overtaken hepatitis C as an indication for liver transplantation in the USA.After liver transplantation,the allograft often develops recurrent NAFLD among patients with known NASH cirrhosis.In addition to recurrent disease,de novo NAFLD has been reported in patients with other indications for liver transplantation.In this review,we will discuss the risk factors associated with recurrent and de novo NAFLD,natural course of the disease,and management strategies after liver transplantation.

Noncanonical intercellular communication in immune response

The classical view of signaling between cells of immune system includes two major routes of intercellular communication:Through the release of extracellular molecules or a direct interaction between membrane bound receptor and its membrane bound ligand,which initiate a cascade of signaling in target cell.However,recent studies indicate that besides these canonical modes of signaling there are also noncanonical routs of intercellular communications through membrane stripping/membrane exchange/trogocytosis,extracellular traps,exosomes and ectososmes/microparticles.In this review we discuss what are the components of noncanonical pathways of signaling and what role they play in immune cells interactions.

Viral hepatitis:A narrative review of hepatitis A–E

Viral hepatitis continues to be a major health concern leading to hepatic decompensation ranging from acute hepatitis to cirrhosis and hepatocellular carcinoma.The hepatic and extrahepatic manifestations are not only debilitating but also associated with a significant economic burden.Over the last two decades,the field of virology has made significant breakthroughs leading to a better understanding of the pathophysiology of viral hepatitis,which in turn has led to new therapeutic options.The advent of direct-acting antiviral agents changed the landscape of hepatitis C virus(HCV)therapy,and new drugs are in the pipeline for chronic hepatitis B virus(HBV)treatment.There has also been a significant emphasis on screening and surveillance programs,widespread availability of vaccines,and linkage of care.Despite these efforts,significant gaps persist in care,and there is a pressing need for increased collaboration and teamwork across the globe to achieve a reduction of disease burden and elimination of HBV and HCV.

A Case of mild idiopathic adulthood ductopenia and brief review of literature

Mild idiopathic adulthood ductopenia(IAD)is a rare cholestatic disease of unknown cause and characterized by interlobular bile duct loss in less than 50%of the portal tracts.We describe the case of a middLe-aged male who presented with persistent elevation of transaminases and alkaline phosphatase.He had a normal biliary tree on endoscopic retrograde cholangiopathy and negative anti-mitochondrial antibody.His liver biopsy specimen showed chronic biliary disease,duct loss in 4 out of 15 portal tracts and prominent cholestasis.Based on the work-up,he likely had mild IAD.Liver transplantation would be necessary if his disease becomes progressive.