Current Status Of Liver Transplantation Research Articles

Current status of liver transplantation for human immunodeficiency virus-infected patients in mainland China

According to the report from the Chinese Center for Disease Control and Prevention, the prevalence of human immunodeficiency virus (HIV) infection exceeded 1.2 million individuals by the year 2022, with an annual increase of about 80000 cases. The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%, almost twice the rate of the general population in China. In addition to the well-documented susceptibility to opportunistic infections and new malignancies, HIV infected patients frequently experience liver-related organ damage, with the liver and kidneys being the most commonly affected. This often leads to the development of end-stage liver and kidney diseases. Therefore, organ transplantation has emerged as an important part of active treatment for HIV infected patients. However, the curative effect is not satisfactory. HIV infection has been considered a contraindication for organ transplantation. Until the emergence of highly active anti-retroviral therapy in 1996, the once intractable replication of retrovirus was effectively inhibited. With prolonged survival, the failure of important organs has become the main cause of death among HIV patients. Therefore, transplant centers worldwide have resumed exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion. This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation (LT) in mainland China. To date, our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV, and all but one, who died two months postoperatively due to sepsis and progressive multi-organ failure, have survived. Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions, cytomegalovirus infection, bacteremia, pulmonary infections, acute kidney injury, new-onset cancers, or vascular and biliary complications.

Current Status of Liver Transplantation in Guatemala

Current Status of Liver Transplantation in Guatemala

[Current status of liver transplantation for adult patients with acute-on-chronic liver failure].

Acute-on-chronic liver failure(ACLF) is the most severe form of acute decompensation that develops in patients with chronic liver disease or liver cirrhosis,and is always accompanied by one or more extrahepatic organ failure, and has an extremely poor short-term prognosis. The causes triggering ACLF are complex and diverse,and the clinical stage and the type and the definition of organ failure differ greatly from one another. Therefore, a universally accepted diagnostic criteria for ACLF is not to be defined, and the epidemiological data and patient outcomes on ACLF are not easy to predict and compare among different regions. Accumulating evidence has shown that liver transplantation(LT) plays a significant role in the surgical treatment of patients with ACLF,but its clinical value is still controversial. The specific management and treatment strategy after the admission of patients with ACLF has not yet formed a unified and standardized process or opinions, which includes the monitoring in the ICU,the support and maintenance of organ functions, the selection of the surgical indication and the timing for LT and so on. Moreover, there still exists many controversies concerning, for example, whether patients with ACLF should receive greater priority for organ allocation compared to other potential candidates on the waiting list. Besides, more prospective controlled studies are urgently needed to investigate the role of the artificial liver support system in the bridging therapy to LT. The aim of this article is to review the indication selection of patients with ACLF suitable for LT,the survival outcomes and prognostic factors after LT, the selection of timing, the organ allocation policy and the bridging therapy to LT, which intends to provide new direction for designing the future clinical studies on LT in patients with ACLF.

Current status of liver transplantation for cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the second most common liver cancer with a median survival of 12-24 mo without treatment. It is further classified based on its location into intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA. Surgical resection is the mainstay of treatment, but up to 70% of these tumors are inoperable at the time of diagnosis. CCA was previously an absolute contraindication for liver transplantation (LT) due to poor outcomes primary due to early recurrent disease. However, improvement in patient selection criteria and neoadjuvant treatment protocols have improved outcomes for inoperable pCCA patients with recent studies reporting LT may improve survival in iCCA. Future advances in the treatment of CCA should include refining patient selection criteria and organ allocation for all subtypes of CCA, determining effective immunotherapies and the evolving role of personalized medicine in patients ineligible for surgical resection or LT. Our article reviews the current status of LT in CCA, along with future directions in managing patients with CCA.

OP-4 Current status of Liver transplantation in Latin America: The Latin-American ALEH special interest group, international Survey 2020

Latin America (LA), is a geographical region with 20 countries homing 652 million people (10% world population), with a huge cultural, economic and developmental diversity. The ALEH (Asociación Latinamericana para el Estudio del Hígado) has driven the formation of a special interest groups (SIGs) to enhance the collaboration of health care professionals with common specialized interests in the field of hepatology. Aims To increase knowledge of the current situation of liver transplantation (LT) in LA, and share experiences between countries. During 2020, LA countries, were invited to nominate representatives to this SIG and also from the STALYC. Online ZOOM meetings were arranged to discuss a survey with more than 70 questions in relation to LT. A database with all the information was built in an excel file. 15 out of 20 countries completed the questionnaire by Jan/2021, representing the situation of 569 million inhabitants. The mean GDP (gross domestic product) per capita in 2019, was 14,573 USD, and the mean health expenditure was 6,3% of the GDP (1,6%-10,4%). Despite the lack of resources in LA, LT started early (Brazil: 1968) and currently 3,837 a total of LT are performed each year, with 12,5% with living donors (n=483). Over the last 50 years, 34,029 total LT have been performed in LA. 13 out of 15 countries (84%) perform DDLT and only 7 countries (46%) also LDLT. The allocation system is based in the MELD/MELD-Na system. The mean waiting time for cirrhotic patients is 276 days (with a waiting list mortality of 10-50%). The mean overall survival at 1 and 5 years after LT is 79,3% and 71,9%, which is similar to developed countries. Access to LT in the region is very heterogeneous, with limited centers and resources to perform LT. Financial, human and material issues, a legal framework favoring organ donation and the procurement structure constitutes a major challenge to improve LT in LA. The collaborative sharing of experiences between countries and centers, may favor the development of guidelines for the region stimulating government initiatives to improve LT access, favoring justice and equity for patients with advanced liver diseases.

Current status of liver transplantation in Europe

Liver transplantation (LT) in Europe became an established life-saving treatment for patients with end-stage liver disease, hepatocellular carcinoma, and acute liver conditions with life-threatening hepatic dysfunction. Although there are substantial disparities in donation and transplant rates among European countries, LT can be offered to almost every European citizen today. In order to maximize the LT benefit beyond national levels, many countries cooperate within transnational organizations including Eurotransplant, Scandiatransplant, and Southern Alliance for Transplantation. In the majority of European countries, liver allocation is based on the Model for End-Stage Liver Disease (MELD). Similar to North America, the ongoing extinction of hepatitis C and increase of non-alcoholic steatohepatitis are also a hallmark of change in LT indications in Europe. Apart from Turkey, the organ pool for LT in European countries is mainly based on organs from donors after brain death, although some countries retrieve a substantial proportion of organs from donors after circulatory death. According to the 2018 report of the European Liver Transplant Registry, 146,762 LT have been performed in Europe until 2016. In the most recent period, LT in Europe achieved respectable 1- and 5-year overall survival rates of 86% and 74%.

Expansion of the hepatocellular carcinoma Milan criteria in liver transplantation: Future directions.

Milan criteria are currently the benchmark related to liver transplantation (LT) for hepatocellular carcinoma. However, several groups have proposed different expanded criteria with acceptable results. In this article, we review the current status of LT beyond the Milan criteria in three different scenarios-expanded criteria with cadaveric LT, downstaging to Milan criteria before LT, and expansion in the context of adult living donor LT. The review focuses on three main questions: what would the impact of the expansion beyond Milan criteria be on the patients on the waiting list; whether the dichotomous criteria (yes/no) currently used are appropriate for LT or continuous survival estimations, such as the one of “Metroticket” and whether it should enter into the clinical practice; and, whether the use of living donor LT in the context of expansion beyond Milan criteria is justified.

Alcohol, liver disease, and transplantation

Review the current status of liver transplantation for patients with alcohol use disorder (AUD). Alcohol-related liver disease (ALD) will increase as a source of patients requiring liver transplantation. Attitudes to use of liver transplantation as rescue therapy for patients with severe alcohol-related hepatitis are changing. The long-term health of ALD liver transplantation recipients requires continued assistance to patients with AUD. Liver transplantation of patients with ALD increased during the last decade and we predict that this trend will continue because of the decline in the number of hepatitis C virus-infected candidates. Concomitantly, a shift in the selection for liver transplantation has occurred of patients with severe alcohol-related hepatitis not responding to medical therapy. Although rescue liver transplantation is a valuable option for patients with severe alcohol-related hepatitis, worldwide practice regarding rescue liver transplantation remains very heterogeneous. There is increasing recognition that excessive consumption of alcohol after liver transplantation is harmful to graft function and patient survival. Factors associated with relapse are younger age at liver transplantation and shorter duration of sobriety prior to liver transplantation. The long-term health of the ALD liver transplant recipient requires continued assistance regarding AUD, a lifelong disorder of craving, relapse, and remission. However, there have been very few studies evaluating best practices for long-term addiction care in transplant recipients. After liver transplantation, the prevalence of cardiovascular disease, infections, and cancer increases over time. Addiction to tobacco constitutes an important issue that must be considered as tobacco cessation may decrease the incidence of tobacco-related cardiovascular and lung disease and aerodigestive cancers.

The New Era of Transplant Oncology: Liver Transplantation for Nonresectable Colorectal Cancer Liver Metastases.

Colorectal cancer (CRC) is the third most incident cancer worldwide. Most of CRC patients will develop distant metastases, mainly to the liver, and liver resection is the only potential chance for cure. On the other hand, only a small proportion of patients with hepatic CRC metastasis are candidates for upfront liver resection. Liver transplantation (LT) is an attractive option for patients with nonresectable CRC liver metastases (NRCLM) without extrahepatic involvement. Initial experiences with LT for NRCLM achieved very poor outcomes, with a 5-year overall survival (OS) lower than 20%. However, these initial studies did not have a standardized patient selection or neoadjuvant or adjuvant therapies. With recent advances in the surgical and medical oncology fields, the landscape has changed. Recent studies from Norway have shown an encouraging 5-year OS of 50% when transplanting patients with NRCLM. Nevertheless, the main concern when expanding the indications for LT is organ shortage. To manage this organ shortage, strategies utilizing live donor liver transplantation are gaining favor. A few ongoing trials are assessing the impact of LT in NRCLM patient survival. Therefore, the aim of this paper is to review the current status of LT for NRCLM.

Liver Transplantation in Latin America

We reviewed the current status of liver transplantation in Latin America. We used data from the Latin American and Caribbean Transplant Society and national organizations and societies, as well as information obtained from local transplant leaders. Latin America has a population of 589 million (8.5% of world population) and more than 2,500 liver transplantations are performed yearly (17% of world activity), resulting in 4.4 liver transplants per million people (pmp) per year. The number of liver transplantations grows at 6% per year in the region, particularly in Brazil. The top liver transplant rates were found in Argentina (10.4 pmp), Brazil (8.4 pmp), and Uruguay (5.5 pmp). The state of liver transplantation in some countries rivals those in developed countries. Model for End-Stage Liver Disease-based allocation, split, domino, and living-donor adult and pediatric transplantations are now routinely performed with outcomes comparable to those in advanced economies. In contrast, liver transplantation is not performed in 35% of Latin American countries and lags adequate resources in many others. The lack of adequate financial coverage, education, and organization is still the main limiting factor in the development of liver transplantation in Latin America. The liver transplant community in the region should push health care leaders and authorities to comply with the Madrid and Istambul resolutions on organ donation and transplantation. It must pursue fiercely the development of registries to advance the science and quality control of liver transplant activities in Latin America.

Liver transplantation for intra- and extrahepatic cholangiocarcinoma

Cholangiocarcinoma (CCA) is the second most frequent primary liver malignancy. Despite extensive surgical approaches and recently developed perioperative chemotherapeutic protocols the 5-year- survival rates range from 20-60%. Especially for central intrahepatic CCA resection is often impossible due to bilobar vascular and biliary invasion; patients with primary sclerosing cholangitis often present with small central tumors and significantly impaired liver function. For these patients liver transplantation (LT) has been discussed as a potential curative option. After a series of LT for CCA in the 1990s with high quotas of early tumor recurrence and very limited long-term survival CCA has widely been agreed upon as a contraindication for LT in times of universal organ shortage. However, in selected cases of patients with PSC and small CCA as well as irresectable Klatskin tumor without extrahepatic disease LT has been performed with acceptable recurrence-free survival rates. Modern, aggressive protocols of perioperative treatment have been established with promising results. This article provides an update and overview on the current status of LT as a potential option for patients with irresectable CCA.

Current status of liver transplantation.

Liver transplantation (LTx) is the treatment of choice for patients with end-stage liver disease (ESLD). Improvement in outcomes (allograft and patient survival) has led to widespread use of LTx worldwide. However, new problems that include severe organ shortage, recurrence of primary disease, opportunistic infections, and development of de novo malignancies are the major problems affecting further implementation of LTx.

Liver transplantation for Wilson disease

The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD.

Current Status of Liver Transplantation in Japan

Current Status of Liver Transplantation in Japan

Liver Transplantation in the United States, 1999-2008

Changes in organ allocation policy in 2002 reduced the number of adult patients on the liver transplant waiting list, changed the characteristics of transplant recipients and increased the number of patients receiving simultaneous liver-kidney transplantation (SLK). The number of liver transplants peaked in 2006 and declined marginally in 2007 and 2008. During this period, there was an increase in donor age, the Donor Risk Index, the number of candidates receiving MELD exception scores and the number of recipients with hepatocellular carcinoma. In contrast, there was a decrease in retransplantation rates, and the number of patients receiving grafts from either a living donor or from donation after cardiac death. The proportion of patients with severe obesity, diabetes and renal insufficiency increased during this period. Despite increases in donor and recipient risk factors, there was a trend towards better 1-year graft and patient survival between 1998 and 2007. Of major concern, however, were considerable regional variations in waiting time and posttransplant survival. The current status of liver transplantation in the United States between 1999 and 2008 was analyzed using SRTR data. In addition to a general summary, we have included a more detailed analysis of liver transplantation for hepatitis C, retransplantation and SLK transplantation.

Current status of liver transplantation for liver cirrhosis and unsolved problem

Current status of liver transplantation for liver cirrhosis and unsolved problem

Current Status of Liver Transplantation

Current Status of Liver Transplantation

Current status of liver transplantation across ABO blood-type barrier

Outcomes of ABO-blood type incompatible liver transplantation have recently improved owing to various treatments. The typical clinical manifestations of antibody mediated rejection (AMR) are hepatic necrosis and intrahepatic biliary complication (IHBC). The prognosis of AMR is poor. AMR is the result of circulatory disturbance which is caused by injury to the endothelium due to an antibody-antigen-complement reaction. Diffuse C4d staining in the portal capillaries and periportal areas in severe AMR. Since natural antibodies against A/B carbohydrate determinants are likely to develop as a result of exposure to environmental bacteria that express similar determinants, the B-1 lineage has been speculated to be the major population of B-cell types responding to A/B determinants. Calcineurin inhibitors block B-1 cell differentiation. Rituximab can be used to deplete both cells that are producing IgM antibodies and those that have already differentiated into B-1 cells. Mycophenolate mofetil is required to inhibit the production of IgG subclass of antibodies. The outcome is now similar to that of blood-type-matched transplantation. However, there are still issues to be solved in order to further improve the outcome via a decrease of infection.

HCV and pregnancy: is now the time for universal testing?

Future VirologyVol. 3, No. 1 EditorialFree AccessHCV and pregnancy: is now the time for universal testing?Steven A Pergam, Stephen E Hawes, Carolyn M Gardella & Chia C WangSteven A Pergam† Author for correspondenceDepartment of Medicine, University of Washington, Fred Hutchinson Cancer Center, 1100 Fairview Ave. North, D3-100, PO Box 19024, Seattle, WA 98109, USA. Search for more papers by this authorEmail the corresponding author at spergam@fhcrc.org, Stephen E HawesUniversity of Washington, Department of Epidemiology, WA, USASearch for more papers by this author, Carolyn M GardellaUniversity of Washington, Department of Obstetrics and Gynecology, WA, USASearch for more papers by this author & Chia C WangVirginia Mason Hospital, Department of Medicine, WA, USASearch for more papers by this authorPublished Online:17 Dec 2007https://doi.org/10.2217/17460794.3.1.1AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Hepatitis C virus (HCV) affects up to 3% of the world’s population [1]. Chronic infection occurs in most HCV-infected patients, causing end-stage liver disease in approximately 20% [2]. Intravenous drug use (IVDU) is the most common risk factor, accounting for 60–80% of cases in the USA. In those without history of IVDU, sexual, household and iatrogenic risk factors are likely modes of transmission [3,4].Approximately 1.6% of the US population is estimated to be HCV-antibody-positive, but prevalence depends on age and other characteristics of the population [5]. For example, the prevalence in active IV drug users is 80–100% [6]. Seroprevalence rates in pregnant women generally range from 0.6 to 2% [7], but may be as high as 4.4% in inner-city populations [8]. An estimated 40,000 women chronically infected with HCV become pregnant every year in the USA.The Centers for Disease Control and Prevention (USA) and the American College of Obstetricians and Gynecologists (ACOG) recommend testing at-risk pregnant women for HCV as part of prenatal care. Testing is encouraged for pregnant women with any history of IVDU, those working in high-risk settings, or those with HIV or hepatitis B infection. Women who received a blood transfusion or solid organ transplant before July 1992, received clotting factor concentrates before 1987, underwent long-term dialysis, and those with signs or symptoms of liver disease should also be tested [9,10].While most experts agree with these recommendations, others advocate for universal HCV testing in pregnancy. In this editorial we address arguments for and against universal testing in the context of recently published data. In the process we review potential complications associated with HCV in pregnancy, identify areas for future research and emphasize the importance of adequate screening in practice.Arguments for universal testingArguments for universal testing of pregnant women focus on; • The inaccuracy of self-reported drug use in pregnant women• The prevalence of non-IVDU modes of transmission in pregnant woman• Inconsistencies in provider screening for HCV-related risk factors and HCV infection• The benefits of early detection.Current recommendations depend on the ability to identify at-risk women. Practitioners face challenges identifying these women, particularly in regards to recreational drug use. In high-risk nonpregnant populations for example, under-reporting of drug use can bias prevalence estimates [11]. Eliciting such information in pregnant women may be further hampered by perceived consequences such as legal ramifications and potential loss of custody, leading to inaccurate responses to screening questions. Unsurprisingly, studies demonstrate that self-reporting is an unreliable method to determine drug use in pregnancy [12–14].Rates of IVDU in HCV-positive pregnant women range between 32 and 50% [15–18], less than the 60–80% reported in HCV-positive patients in the general population [19]. These figures suggest pregnant women may be more likely to acquire HCV infection through non-IVDU exposures. An increased risk of HCV in pregnant women living with partners with HCV or an IVDU history suggests a larger role for sexual or household transmission [17,20]. Even more troubling, up to 40% of pregnant women may have no identifiable risk factor [15].Obstetricians may also miss opportunities to test at-risk women for HCV. In one study, less than 50% of obstetricians recommended testing patients with histories of IVDU, and only 30% for patients who had recieved blood transfusions prior to 1992 [21]. Furthermore, while 60% of Australian gynecologists routinely tested for HCV, only 20% routinely asked about risk factors for blood-borne infections [22]. Local rates of HCV and HIV, misconceptions about HCV and limited HCV treatment options may influence a provider’s likelihood for following testing guidelines.Universal testing has the advantage of identifying women not captured by current guidelines. Pregnancy is an opportunity to identify women with HCV, many of whom may not have otherwise sought, nor had access, to primary care. Since few are aware of their serologic status [23], early diagnosis could be the most important reason in support of universal testing for HCV. Those identified as HCV-positive could benefit from opportunities for evaluation and treatment, alcohol abstinence and access to primary care and monitoring.Arguments against universal testingSince 2–4% of HCV-infected mothers transmit infection to their infants perinatally [7], universal testing would be more strongly advocated if knowledge of maternal status could decrease this risk. Therapy for HCV in pregnancy is currently not recommended due to the potential teratogenicity of current treatment agents [24]. Furthermore, unlike the case for HIV, cesarean section has not been shown to decrease rates of vertical transmission. A few studies suggest decreased rates of perinatal HCV transmission with cesarean section [25], but a large metanalysis found no protective benefit [26].Others have indicated an increase in HCV transmission through invasive monitoring and prolonged rupture of membranes [27,28], but these findings are debated [25]. Additionally, breastfeeding has not been shown to increase the risk of transmission [29]. If prevention of vertical transmission is a primary goal of early testing, the lack of effective interventions argues against more rigorous efforts to detect maternal HCV infection.Pregnancy does not appear to impact HCV disease progression, as evidenced by the lack of changes in liver function or level of viremia during pregnancy [30,31]. Perinatally-acquired HCV is also relatively asymptomatic during childhood. In the first year of life greater then 50% of children have elevated liver function tests [32,33], but early clinical symptoms are rare. HCV viremia clears in up to 25% of infected children [33,34]. Hepatic fibrosis and/or minimal to mild hepatitis is present in nearly 75% of infected children on liver biopsy [33,35,36], but progression to cirrhosis and liver transplantation due to HCV during childhood is rare [37]. Information on the progression of disease into adulthood in perinatally-infected children is currently lacking.While data do not support adverse consequences of pregnancy on the course of HCV infection in mothers, and support a benign natural history for children infected at birth, few studies have examined peripartum effects of HCV infection on maternal and neonatal health. The limited data that are available come to varying conclusions. While maternal HCV was not associated with obstetric complications in a number of studies [23,38,39], one reported that women with HCV viremia had an increased risk of premature rupture of membranes [40]. Two studies demonstrated an increased risk of gestational diabetes in pregnant women with HCV [41,42]. While the known association of HCV infection with insulin resistance in nonpregnant persons [43] suggests a potential biologic plausibility to these observations, further study is needed to confirm these findings.Data regarding the effect of HCV on neonatal outcomes is also contradictory. Two studies found no difference in rates of prematurity in children born to HCV-positive women [20,39], while another demonstrated higher rates of prematurity and spontaneous abortion in women with acute hepatitis [44]. A study in HIV-positive women demonstrated higher rates of low birth weight children (<2500 g) born to those coinfected with HCV [42], and another demonstrated higher rates of neonatal intensive care unit admission and need for assisted ventilation [41]. Apgar scores on the other hand, appear to be similar regardless of maternal HCV status [20,23,38,41]. Owing to their narrow scope and retrospective nature, conclusions that can be drawn from these studies are limited.Perhaps most importantly, costs of identifying a single pregnant woman using universal testing were estimated to be more than twice that of current standard of care [45]. Universal testing of asymptomatic women is not cost–effective, even when modeled under the assumption that primary cesarean section reduces the risk of perinatal transmission, and when costs associated with chronic infection in the mother are taken into account [46]. Unless the potential risks associated with HCV on peripartum outcomes are substantiated, universal testing does not appear to be cost–effective.Conclusion & future directionsCurrent studies provide insufficient evidence to advocate for universal testing for HCV, but data do suggest that current screening approaches could be improved. Expanding criteria to include testing women with less common risk factors would enhance identification of those missed by current guidelines. Providing optional testing for pregnant women may be more acceptable for patients concerned about self exposure, and could lead to improved detection of high-risk patients. Finally, increased provider education regarding the risk factors for HCV in pregnancy could also maximize identification of at-risk women.Reviewing guidelines for testing pregnant women is particularly timely as newer, more effective antiviral therapy for HCV are currently being developed. Such therapies may render it even more essential to identify HCV in pregnancy. Not only providing the opportunity to counsel about the risk of vertical transmission, early testing would take advantage of this limited period of engagement to identify and potentially eradicate HCV in these women.Further evaluation of the impact of HCV on short- and long-term effects on pregnancy outcomes, longitudinal studies in perinatally acquired infection and treatment options for pregnant women and children are needed. Until then, efforts to increase awareness of the relevance and pitfalls of current recommendations for risk factor driven HCV testing should remain standard care for all providers caring for pregnant women.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.Bibliography1 Wasley A, Alter MJ: Epidemiology of hepatitis C: geographic differences and temporal trends. Semin. Liver Dis.20(1),1–16 (2000).•• Excellent review of the worldwide epidemiology of hepatitis C virus (HCV).Crossref, Medline, CAS, Google Scholar2 Seeff LB: Natural history of hepatitis C. Am. J. Med.107(6B),10S–15S (1999).•• Demonstrates the major negative long-term effects of HCV.Crossref, Medline, CAS, Google Scholar3 Lauer GM, Walker BD: Hepatitis C virus infection. N. Engl. J. Med.345(1),41–52 (2001).•• Major review of HCV disease and pathophysiology.Crossref, Medline, CAS, Google Scholar4 Wang CC, Krantz E, Klarquist J et al.: Acute hepatitis C in a contemporary US cohort: modes of acquisition and factors influencing viral clearance. J. Infect. Dis.196(10),1474–1482 (2007).• Shows the changes in contemporary modes of HCV acquisition.Crossref, Medline, Google Scholar5 Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ: The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann. Intern. Med.144(10),705–714 (2006).•• The epidemiology of HCV in the USA.Crossref, Medline, Google Scholar6 Murrill CS, Weeks H, Castrucci BC et al.: Age-specific seroprevalence of HIV, hepatitis B virus, and hepatitis C virus infection among injection drug users admitted to drug treatment in 6 US cities. Am. J. Public Health92(3),385–387 (2002).• Reviews the seroprevalance of blood-borne viruses in drug users.Crossref, Medline, Google Scholar7 Roberts EA, Yeung L: Maternal-infant transmission of hepatitis C virus infection. Hepatology36(5 Suppl 1),S106–S113 (2002).•• An excellent review of perinatal HCV transmission.Medline, Google Scholar8 Silverman NS, Jenkin BK, Wu C, McGillen P, Knee G: Hepatitis C virus in pregnancy: seroprevalence and risk factors for infection. Am. J. Obstet. Gynecol.169(3),583–587 (1993).• Demonstrates an increased risk of transmission in an inner-city population.Crossref, Medline, CAS, Google Scholar9 ACOG Committee Opinion No. 357: Primary and preventive care: periodic assessments. Obstet. Gynecol.108(6),1615–1622 (2006).•• Current screening guidelines.Crossref, Medline, Google Scholar10 Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention. MMWR Recomm. Rep.47(RR-19),1–39 (1998).•• Current screening guidelines.Medline, CAS, Google Scholar11 Magura S, Kang SY: Validity of self-reported drug use in high risk populations: a meta-analytical review. Subst. Use Misuse31(9),1131–1153 (1996).Crossref, Medline, CAS, Google Scholar12 Pegues DA, Engelgau MM, Woernle CH: Prevalence of illicit drugs detected in the urine of women of childbearing age in Alabama public health clinics. Public Health Rep.109(4),530–538 (1994).•• Demonstrates the inaccuracy of self-reporting of drug use in pregnant women.Medline, CAS, Google Scholar13 Koren G, Chan D, Klein J, Karaskov T: Estimation of fetal exposure to drugs of abuse, environmental tobacco smoke, and ethanol. Ther. Drug Monit.24(1),23–25 (2002).Crossref, Medline, CAS, Google Scholar14 Sanaullah F, Gillian M, Lavin T: Screening of substance misuse during early pregnancy in Blyth: an anonymous unlinked study. J. Obstet. Gynaecol.26(3),187–190 (2006).Crossref, Medline, CAS, Google Scholar15 Conte D, Fraquelli M, Prati D, Colucci A, Minola E: Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women. Hepatology31(3),751–755 (2000).•• Shows the prevalence of HCV and the high rate of unknown risk factors in pregnant women.Crossref, Medline, CAS, Google Scholar16 Baldo V, Floreani A, Menegon T, Grella P, Paternoster DM, Trivello R: Hepatitis C virus, hepatitis B virus and human immunodeficiency virus infection in pregnant women in North-East Italy: a seroepidemiological study. Eur. J. Epidemiol.16(1),87–91 (2000).Crossref, Medline, CAS, Google Scholar17 Ward C, Tudor-Williams G, Cotzias T, Hargreaves S, Regan L, Foster GR: Prevalence of hepatitis C among pregnant women attending an inner London obstetric department: uptake and acceptability of named antenatal testing. Gut47(2),277–280 (2000).• Reviews prevalence of HCV in pregnancy.Crossref, Medline, CAS, Google Scholar18 Marranconi F, Fabris P, Stecca C et al.: Prevalence of anti-HCV and risk factors for hepatitis C virus infection in healthy pregnant women. Infection22(5),333–337 (1994).Crossref, Medline, CAS, Google Scholar19 Alter MJ, Kruszon-Moran D, Nainan OV et al.: The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N. Engl. J. Med.341(8),556–562 (1999).Crossref, Medline, CAS, Google Scholar20 Bohman VR, Stettler RW, Little BB, Wendel GD, Sutor LJ, Cunningham FG: Seroprevalence and risk factors for hepatitis C virus antibody in pregnant women. Obstet. Gynecol.80(4),609–613 (1992).• Reviews risk factors for HCV positivity in pregnant women.Medline, CAS, Google Scholar21 Boaz K, Fiore AE, Schrag SJ, Gonik B, Schulkin J: Screening and counseling practices reported by obstetrician-gynecologists for patients with hepatitis C virus infection. Infect. Dis. Obstet. Gynecol.11(1),39–44 (2003).•• Demonstrates that obstetricians miss opportunities to screen for HCV.Crossref, Medline, Google Scholar22 Giles ML, Sasadeusz JJ, Garland SM, Grover SR, Hellard ME: An audit of obstetricians’ management of women potentially infected with blood-borne viruses. Med. J. Aust.180(7),328–332 (2004).• Demonstrates that obstetricians miss opportunities to screen for blood-borne viruses.Crossref, Medline, Google Scholar23 Floreani A, Paternoster D, Zappala F et al.: Hepatitis C virus infection in pregnancy. Br. J. Obstet. Gynaecol.103(4),325–329 (1996).Crossref, Medline, CAS, Google Scholar24 Jain S, Goharkhay N, Saade G, Hankins GD, Anderson GD: Hepatitis C in pregnancy. Am. J. Perinatol.24(4),251–256 (2007).]•• Reviews current treatment options for HCV in pregnancy.Crossref, Medline, Google Scholar25 Gibb DM, Goodall RL, Dunn DT et al.: Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission. Lancet356(9233),904–907 (2000).Crossref, Medline, CAS, Google Scholar26 McIntyre PG, Tosh K, McGuire W: Caesarean section versus vaginal delivery for preventing mother to infant hepatitis C virus transmission. Cochrane Database Syst. Rev.4,CD005546 (2006).•• A large metanalysis demonstrating the lack of evidence to recommend cesarean-section in HCV-positive women.Google Scholar27 Mast EE, Hwang LY, Seto DS et al.: Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy. J. Infect. Dis.192(11),1880–1889 (2005).• Shows an increased rate of transmission with invasive monitoring.Crossref, Medline, Google Scholar28 A significant sex – but not elective cesarean section – effect on mother-to-child transmission of hepatitis C virus infection. J. Infect. Dis.192(11),1872–1879 (2005).Crossref, Medline, Google Scholar29 Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. European Paediatric Hepatitis C Virus Network. Br. J. Obstet. Gynaecol.108(4),371–377 (2001).•• Shows no increased perinatally-transmitted HCV associated with mode of delivery.Crossref, Google Scholar30 Paternoster DM, Santarossa C, Grella P et al.: Viral load in HCV RNA-positive pregnant women. Am. J. Gastroenterol.96(9),2751–2754 (2001).• Demonstrates no adverse effects of pregnancy on HCV.Crossref, Medline, CAS, Google Scholar31 Hattori Y, Orito E, Ohno T et al.: Loss of hepatitis C virus RNA after parturition in female patients with chronic HCV infection. J. Med. Virol.71(2),205–211 (2003).• Shows no adverse effects of pregnancy on HCV viral load.Crossref, Medline, CAS, Google Scholar32 Resti M, Jara P, Hierro L et al.: Clinical features and progression of perinatally acquired hepatitis C virus infection. J. Med. Virol.70(3),373–377 (2003).•• Shows that progression to liver disease is uncommon in perinatally acquired disease.Crossref, Medline, Google Scholar33 Jara P, Resti M, Hierro L et al.: Chronic hepatitis C virus infection in childhood: clinical patterns and evolution in 224 white children. Clin. Infect. Dis.36(3),275–280 (2003).•• Shows that perinatally acquired HCV is usually mild.Crossref, Medline, Google Scholar34 The European Paediatric Hepatitis C Network: Three broad modalities in the natural history of vertically acquired hepatitis C virus infection. Clin. Infect. Dis.41(1),45–51 (2005).•• Shows that perinatally acquired HCV is usually mild during short-term follow up.Crossref, Medline, Google Scholar35 El-Hawary MA, El-Raziky MS, Esmat G et al.: Assessment of hepatic fibrosis in pediatric cases with hepatitis C virus in Egypt. World J. Gastroenterol.13(20),2846–2851 (2007).• Demonstrates minimal liver disease on biopsy in children with perinatally-acquired HCV.Crossref, Medline, CAS, Google Scholar36 Bortolotti F, Resti M, Giacchino R et al.: Hepatitis C virus infection and related liver disease in children of mothers with antibodies to the virus. J. Pediatr.130(6),990–993 (1997).Crossref, Medline, CAS, Google Scholar37 McDiarmid SV: Current status of liver transplantation in children. Pediatr. Clin. North Am.50(6),1335–1374 (2003).• Demonstrates minimal long-term evidence of need for transplantation in children due to perinatally aquired disease.Crossref, Medline, CAS, Google Scholar38 Jabeen T, Cannon B, Hogan J et al.: Pregnancy and pregnancy outcome in hepatitis C type 1b. QJM93(9),597–601 (2000).• Shows no increase in adverse pregnancy outcomes in those with maternal HCV.Crossref, Medline, CAS, Google Scholar39 Jaffery T, Tariq N, Ayub R, Yawar A: Frequency of hepatitis C in pregnancy and pregnancy outcome. J. Coll. Physicians Surg. Pak.15(11),716–719 (2005).• Shows no adverse outcomes associated with maternal HCV.Medline, Google Scholar40 Latt NC, Spencer JD, Beeby PJ et al.: Hepatitis C in injecting drug-using women during and after pregnancy. J. Gastroenterol. Hepatol.15(2),175–181 (2000).• Shows no adverse outcomes associated with maternal HCV.Crossref, Medline, CAS, Google Scholar41 Pergam SA, Wang CC, Gardella CM, Sandison TG, Phipps WT, Hawes SE: Adverse maternal and neonatal outcomes associated with maternal hepatitis C infection in pregnancy. Presented at: Infectious Diseases Society of America 45th Annual Meeting. San Diego, CA, US, 4–7 November 2007.• Demonstrates increased rates of adverse peripartum outcomes in those with maternal HCV.Google Scholar42 Marti C, Pena JM, Bates I et al.: Obstetric and perinatal complications in HIV-infected women. Analysis of a cohort of 167 pregnancies between 1997 and 2003. Acta Obstet. Gynecol. Scand.86(4),409–415 (2007).• Demonstrates increased rate of gestational diabetes and low birth weight infants in women with HCV-HIV coinfection compared to women with HIV only.Crossref, Medline, Google Scholar43 Shintani Y, Fujie H, Miyoshi H et al.: Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology126(3),840–848 (2004).Crossref, Medline, CAS, Google Scholar44 Medhat A, el-Sharkawy MM, Shaaban MM, Makhlouf MM, Ghaneima SE: Acute viral hepatitis in pregnancy. Int. J. Gynaecol. Obstet.40(1),25–31 (1993).Crossref, Medline, CAS, Google Scholar45 Leikin EL, Reinus JF, Schmell E, Tejani N: Epidemiologic predictors of hepatitis C virus infection in pregnant women. Obstet. Gynecol.84(4),529–534 (1994).Medline, CAS, Google Scholar46 Plunkett BA, Grobman WA: Routine hepatitis C virus screening in pregnancy: a cost-effectiveness analysis. Am. J. Obstet. Gynecol.192(4),1153–1161 (2005).•• Shows that routine HCV testing in pregnant women is not cost-effective.Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited ByCDC Recommendations for Hepatitis C Screening Among Adults — United States, 202010 April 2020 | MMWR. Recommendations and Reports, Vol. 69, No. 2Hepatitis C Virus universal screening versus risk based selective screening during pregnancyJournal of Neonatal-Perinatal Medicine, Vol. 8, No. 4 Vol. 3, No. 1 Follow us on social media for the latest updates Metrics History Published online 17 December 2007 Published in print January 2008 Information© Future Medicine LtdFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. 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Liver Transplantation for Hepatocellular Carcinoma in Asia

Hepatocellular carcinoma (HCC) is a leading cause of cancer death, particularly in Asia where the major etiology, chronic hepatitis B virus infection, is endemic. The tumor frequently develops in a background of cirrhosis, and liver transplantation offers a chance to cure both the tumor and the underlying cirrhosis. The Milan criteria based on tumor size and number as an estimate of tumor burden are conventionally the gold standard in determining eligibility for transplantation, and the outcome is excellent. The shortage of organs from deceased donors has curtailed the adoption of extended criteria and led to the problems of long waiting times and dropouts. Several measures have been taken to tackle these issues, including prioritization of patients with HCC, use of pretransplant adjuvant treatment to prevent tumor progression, and living donor liver transplantation (LDLT). With a high incidence of HCC and a low organ donation rate, Asia has developed a distinctive pattern of indication and strategy in the application of liver transplantation. Over the last decade, the number of liver transplants in Asia has increased rapidly, by 10-fold, largely as a result of the development of LDLT. The proportion of patients who undergo liver transplantation for HCC is increasing and HCC comprises one third of the indication for liver transplantation in Asia. LDLT is the dominant strategy, accounting for 96% of the liver transplants for HCC. Many transplant programs accept patients beyond the Milan criteria, and the reported 3-year survival rate is about 60%. With the promotion of organ donation, better quantification of the benefit of LDLT for extended indications, and identification of predictors for survival, the practice of liver transplantation for HCC in Asia will continue to evolve.