Use of a hepatitis C virus (HCV) RNA‐positive donor in a treated HCV RNA‐negative liver transplant recipient

The shortage of livers has led most transplant centers to use extended criteria donors. Hepatitis C virus (HCV) RNA‐positive donor organs are typically not given to patients who have cleared HCV. A 64‐year‐old male with chronic hepatitis C, genotype 1b was listed for LT with hepatocellular carcinoma. While on the waiting list, the patient was treated with sofosbuvir, ledipasvir, and ribavirin and achieved an HCV RNA <15 IU/mL by week 10. At week 18 of a planned 24‐week treatment course, the patient underwent deceased‐donor LT and received an organ from an anti‐HCV‐positive donor. Treatment was stopped at LT. At week 3 post LT, HCV RNA was detectable and revealed a genotype 3 HCV infection, compatible with transplantation of an organ with established infection. With retreatment with sofosbuvir, daclatasvir, and ribavirin for 12 weeks, the patient achieved a sustained virologic response. This report highlights how antiviral therapies can be used to optimize the outcomes of HCV‐infected transplant patients.     

Hepatitis C genotype change after transplantation utilizing hepatitis C positive donor organs

A shortage in organs for transplantation has led to the increased use of hepatitis C (HCV) infected donor organs for solid organ transplant recipients infected with HCV. However, the donor HCV genotype is not routinely checked or known prior to transplant. Here, we report 4 cases of genotype conversion after transplantation in patients receiving HCV infected donor organs. This change in genotype may potentially impact HCV progression as well as treatment choice for these patients.     

Successful treatment of donor‐derived hepatitis C viral infection in three transplant recipients from a donor at increased risk for bloodborne pathogens

We report here the successful treatment of hepatitis C virus (HCV) transmitted from a nucleic acid testing (NAT)‐negative donor to three HCV‐negative recipients—two renal transplants and one liver. Both renal recipients underwent standard deceased‐donor renal transplantation with immediate graft function. The liver recipient underwent standard orthotopic liver transplantation and recovered uneventfully. The donor was a 39‐year‐old woman with a terminal serum creatinine of 0.7 mg/dL. She was high risk for bloodborne pathogens, based upon a history of sexual contact with an HCV‐infected male partner. Recipient 1 was a 45‐year‐old man with a history of end‐stage renal disease from systemic lupus erythematosus. Recipient 2 was a 62‐year‐old woman with a history of end‐stage renal disease caused by hypertension and insulin‐dependent diabetes. Recipient 3 was a 42‐year‐old man with acute liver failure from acetaminophen ingestion. All recipients became HCV polymerase chain reaction positive on post‐transplant follow‐up. Both kidney recipients were treated with ledipasvir/sofosbuvir combination therapy for 12 weeks without side effects or rejection episodes. Recipient 3 was treated with ledipasvir/sofosbuvir in combination with ribavirin for 12 weeks without side effects. All patients achieved a sustained viral response at 12 weeks and are considered cured of HCV. The kidney recipients maintained good allograft function with a serum creatinine of 1.4 mg/dL and 1.0 mg/dL, respectively. Both renal recipients maintained normal liver function post treatment and did not develop any evidence of fibrosis. The liver recipient's liver function tests returned to normal without further incident. This case report provides evidence for the successful treatment of donor‐derived HCV in transplant recipients.     

The impact of viral hepatitis‐related hepatocellular carcinoma to post‐transplant outcomes

Hepatocellular carcinoma (HCC) is the most common complication of HCV infection leading to liver transplantation. We evaluated the impact of aetiology of liver disease on patient and graft survival following liver transplantation for HCC. From the Scientific Registry of Transplant Recipients (2002–2011), all adults who underwent liver transplantation for HCC were retrospectively included. Aetiology of liver disease was grouped into HCV, HBV, HCV–HBV co‐infection and nonviral liver disease. Of 8,733 liver transplant recipients with HCC, 5507 had HCV, 631 had HBV, 163 were co‐infected, and 2432 had nonviral causes of liver disease. In follow‐up (48 ± 32 months), 8.2% had graft failure and 29.5% died. The mean rates of graft failure were 9.5%, 4.7%, 6.1% and 6.4% in HCV, HBV, HCV–HBV co‐infection and nonviral liver disease, respectively (P < 0.0001). Post‐transplant mortality rate in patients with HBV was 20.2%, HCV 31.0%, HCV–HBV 28.5% and nonviral 28.5% (P < 0.0001). This difference was significant starting one year post‐transplant and became even more prominent later in follow‐up. Five‐year post‐transplant survival was 64.7% in HCV, 77.7% in HBV, 71.0% in HCV–HBV and 69.1% in nonviral HCC (P < 0.0001). A diagnosis of HCV in patients with HCC was also independently associated with an increased risk of both graft failure (adjusted hazard ratio = 1.84 (1.46–2.33), P < 0.0001) and mortality (1.35 (1.21–1.50), P < 0.0001) in multivariate analysis. Patients with HCV‐related HCC are at higher risk of adverse post‐transplant outcomes. These patients should be considered for preemptive interferon‐free antiviral therapy prior to or immediately following liver transplantation.     

Indications for liver transplantation in patients with chronic hepatitis B and C virus infection and hepatocellular carcinoma

Patients with chronic hepatitis B virus (HBV) infection were not accepted for liver transplantation in Asia in the past because the hepatitis B immune globulin (HBIG) used to prevent post‐transplantation recurrence was very expensive and it was generally believed that Asians with hepatitis B fared worse than Caucasians after liver transplantation. The availability of lamivudine has altered the indication of liver transplantation for these patients. Twenty‐five Chinese patients with chronic HBV infection were given lamivudine as primary prophylaxis against HBV re‐infection before transplantation. Five patients died within 40 days of transplantation. After a median follow‐up period of 14 months (range, 5–39), 17 patients had lost serum HBsAg from 4 days to 27 months post transplantation, but it reappeared in three patients 4–12 months later. Antibody to HBsAg was detected periodically in the serum of 11 patients who had lost HBsAg. At the last follow‐up, six patients were HBsAg‐positive and HBV DNA was detected in only one of them. The indication for liver transplantation for chronic hepatitis C virus (HCV) infection is not as strict as for patients with chronic HBV infection because the long‐term survival is similar to that of non‐hepatitis C patients, even though re‐infection by HCV in the recipients is nearly universal. The main issue in the selection of patients with HCV for liver transplantation is therefore identification of criteria that can predict re‐infection and development of cirrhosis. These include factors such as multiple episodes of rejection, use of OKT3, pre‐transplant viral load and genotype, but reports are not consistent and so there are no well‐defined selection criteria. The selection criteria for patients with hepatocellular carcinoma are now well defined. Many studies have confirmed that a tumour > 5 cm, and showing vascular invasion, and poor differentiation adversely affects survival. In practice, only patients with a tumour < 5 cm and Child’s C cirrhosis are accepted for liver transplantation. Transarterial oily chemoembolization and intralesional alcohol injection are used to control or down‐stage the tumour while patients wait for a cadaveric liver graft.     

Successful heart‐kidney transplantation from a Hepatitis C viremic donor to negative recipient: One year of follow‐up

Every year the number of patients waiting for a heart transplant increases faster than the number of available donor organs. Some potential donor organs are from donors with active communicable diseases, including hepatitis C virus (HCV), potentially making donation prohibitive. The advent of direct‐acting antiviral agents for HCV has drastically changed the treatment of HCV. Recently, these agents have been used to treat HCV in organ donor recipients who acquired the disease from the donor organ. We report a case of heart‐kidney transplantation from an HCV viremic donor to HCV negative recipient with successful treatment and sustained virologic response.     

Utilization of increased risk for transmission of infectious disease donor organs in solid organ transplantation: Retrospective analysis of disease transmission and safety

The inadequate supply of transplantable organs necessitates new approaches to organ availability. Serologies and nucleic acid testing (NAT) for hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) are used in microbiologic screening of potential organ donors. Organs from donors considered at “high risk” (Centers for Disease Control and Prevention, CDC 1994) or “increased risk” (U.S. Public Health Service, PHS 2013) for transmission of viral infection to recipients may provide an expanded source of organs for transplantation. We review a single‐center experience with 257 adult organ recipients of organs from donors meeting either CDC 1994 or PHS 2013 risk criteria between 2011 and 2016. Tracking these transplants required modification of the Transplant Center electronic database to identify all recipients of increased‐risk donor (IRD) organs, documentation of informed consent, and microbiologic testing data. No transmissions of HIV, HBV, or HCV were identified by NAT or clinically. Nine patients developed positive serologic assays for one of the tested viruses; all recipients were retested and remain negative by NAT. Notably, post‐transplant HBV core serologies reverted to negative on re‐testing; these positive serologies are likely false positives caused by receipt of blood products. Use of IRD organs can be performed safely with appropriate informed consent and rigorous pre‐ and post‐transplant microbiological testing.     

Double lung transplantation in an HIV‐positive patient with Mycobacterium kansasii infection

Good outcomes with kidney and liver transplantation in HIV‐positive patients have led clinicians to recommend lung transplantation in HIV‐positive patients based on extrapolated data. Pre‐transplant mycobacterial infection is associated with an increased risk of developing new infection or aggravating existing infection, though it does not contraindicate transplantation in non‐HIV–infected patients. However, no data exists regarding the outcome of HIV‐positive patients with pre‐transplant mycobacterial infection. We report a case of double lung transplantation in a 50‐year‐old HIV‐positive patient with alpha‐1 antitrypsin deficiency. Prior to transplantation, Mycobacterium kansasii was isolated in one sputum culture and the patient was considered merely colonized as no clinical evidence of pulmonary or disseminated disease was present. The patient successfully underwent a double lung transplantation. Nontuberculous mycobacterial infection was diagnosed histologically on examination of native lungs. Surveillance and watchful waiting were chosen over treatment of the infection. HIV remained under control post‐transplantation with no AIDS‐defining illnesses throughout the follow‐up. A minimal acute rejection that responded to increased corticosteroids was reported. At 12 months post‐transplant, a bronchiolitis obliterans syndrome was diagnosed after a drop in FEV1. No evidence of isolation nor recurrence of nontuberculous mycobacteria was reported post‐transplantation. At 15 months post‐transplant, the patient remained stable with an FEV1 of 30%. The presence of pre‐transplant nontuberculous mycobacterial infection did not translate into recurrence of nontuberculous mycobacterial infection post‐transplant. Whether it contributed to bronchiolitis obliterans syndrome remains unknown.     

Retrospective evaluation of the risk of hepatitis B virus reactivation after transplantation

Abstract: Numerous case reports describe patients with previously documented immunity developing active hepatitis B virus (HBV) infection after transplantation. However, the risk of reactivation of HBV under long‐term immunosuppression in hepatitis B core antibody (HBcAb)‐positive, hepatitis B surface antigen (HBsAg)‐negative transplant recipients has not been clearly described. Herein, we present a long‐term follow‐up for 49 HBcAb‐positive, HBsAg‐negative recipients (27 liver, 18 kidney, 4 pancreas) transplanted between June 1996 and April 2001. Among these, 37 recipients (76%) were HBsAb positive at transplantation. Immunosuppression consisted of various antibody induction regimens in 20 (41%) of the recipients with either tacrolimus (33 [67%])‐ or cyclosporine (16 [33%])‐based maintenance immunosuppression. The incidence and duration of HBV prophylaxis was not significant. No patient received hepatitis B immunoglobulin (HBIG) before or after transplantation. Additionally, only two patients received lamivudine, which was started post transplant without clinical indication. The mean length of follow‐up was 3.1±1.4 years. At the last follow‐up, overall patient and graft survival were 98% and 96%, respectively. Patient survival was 96% in liver, 100% in kidney, and 100% in pancreas transplant recipients. The graft survival for each organ type was 93% in liver, 100% in kidney, and 75% in pancreas transplant recipients at the end of follow‐up. There was no incidence of HBV reactivation defined as recurrence of HBsAg and/or HBV DNA positivity. These data suggest that the risk of reactivation of HBV in HBcAb‐positive, HBsAg‐negative transplant recipients under immunosuppression is negligible, regardless of immunosuppressive regimen, lamivudine prophylaxis, or HBsAb status. These patients should have access to transplantation as they enjoy excellent patient and graft survival rates.     

Liver‐specific deceased donor risk indices

In order to assess the quality of the donor liver, procuring surgeons should accurately evaluate not only general donor risk indices, such as donor age, causes of brain death and cold ischemic time, but also consider the specific donor risk indices. In this review, we focus on liver‐specific deceased donor risk indices, including liver steatosis, anti‐hepatitis B core (HBc) positive or hepatitis C virus (HCV) positive donors, hypernatremia and anatomical variations. Liver steatosis is strongly associated with poor graft function after liver transplantation. Liver with more than 40–50% macrosteatosis should not be used. However, at present the quantity of fatty livers lack accepted standards. The computerized image analysis programs should be used to automate the determination of fat content in liver biopsy specimens. Liver grafts from anti‐HBc positive donors can be safely used, preferentially in hepatitis B surface antigen (HBsAg) positive or anti‐HBc/anti‐HBs positive recipients. HCV positive allografts free from fibrosis or severe inflammation are a safe option for HCV positive recipients. The procurement team should consider liver biopsy to evaluate these HCV positive allografts. Donor serum sodium over 150 mm may predict a higher rate of graft primary non‐functions. Recently, however, some investigators reported the sodium level likely has little clinical impact on post‐transplant liver function. The incidence of hepatic artery variations has been reported to be approximately 30%. To avoid injuries, it is very important to know and identify these variations with precision at the time of organ procurement.     

Outcomes of transplantation using organs from a donor infected with Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae

Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi‐organ infection with Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae. Recipient 1 underwent simultaneous liver and kidney transplantation for alpha‐1 antitrypsin deficiency and alcohol‐related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC‐producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living‐donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC‐producing K. pneumoniae. Culture of the preservation fluid containing the vein graft was positive for KPC‐producing K. pneumoniae. The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed‐field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC‐producing K. pneumoniae. All transplant recipients had good short‐term outcomes. These cases highlight the importance of inter‐institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug‐resistant organisms.     

Asymptomatic transmission of Treponema pallidum (syphilis) through deceased donor liver transplantation

A 55‐year‐old woman underwent liver transplantation (LT) with a graft from a deceased donor. Mandatory pre‐donation investigations showed positive syphilis serology that was available only after the transplant, with high Treponema pallidum particle agglutination assay titer compatible with donor syphilis infection. Despite the institution of appropriate post‐exposure prophylaxis, the recipient demonstrated latent seroconversion; however, liver graft function improved without evidence of syphilitic hepatitis or other manifestations of the disease. Through this first reported case of asymptomatic transmission of syphilis following LT, we highlight the investigations and treatment strategies for donor‐derived syphilis in liver transplant recipients. This report supplements the existing limited evidence on safe use of infected grafts from syphilitic donors through appropriate post‐exposure prophylaxis.     

Kidney transplantation from an HIV‐positive cadaveric donor

Kidney transplantation is the gold‐standard therapy for select HIV‐positive patients with ESRD. Since the Italian Ministry of Health defined the guidelines for organ donation from HIV‐positive persons in 2018, we report the first case of renal transplantation from an HIV‐positive cadaveric donor in two HIV‐positive recipients in Italy. The donor was a 50‐year‐old male, deceased due to post‐anoxic encephalopathy, with a history of HIV infection in HAART, undetectable viral load, and HCV‐related chronic hepatitis that had been previously treated. The first recipient was a 59‐year‐old female with a prior history of drug addiction, and she suffered from ESRD secondary to HIV nephropathy. The patient followed preoperative HAART with a good viral response and undetectable HIV viral load. She also had a history of HCV‐related chronic hepatitis that had been successfully treated. The right kidney was uneventfully transplanted. The patient developed an asymptomatic reinfection of endogenous BK virus. The second recipient was a 41‐year‐old male with ESRD secondary to polycystic kidney disease. The patient was HIV‐positive in HAART, with a good viro‐immunologic response and an undetectable HIV viral load. He suffered from a severe form of hemophilia A and HCV‐related chronic hepatitis, which had been previously treated with undetectable HCV RNA. The left kidney was uneventfully transplanted. At the end of follow‐up, both patients had a healthy condition with stable renal function, a persistently good viral response and undetectable HIV and HCV viral loads. These encouraging preliminary results seem to confirm the safety and effectiveness of kidney transplantation from select HIV‐positive donors.     

Chronic hepatitis C and chronic kidney disease: Advances,limitations and unchartered territories

Over the past few years, treatment options for chronic hepatitis C virus (HCV) infection have evolved dramatically. The current approved interferon‐free direct‐acting antiviral (DAA) regimens have been shown to be safe and effective with sustained virologic response (SVR) rates of >90% in most patients. Unique issues yet remain such as the challenges in patients with impaired renal function or decompensated cirrhosis. Patients with stages 4‐5 chronic kidney disease (CKD) have a higher prevalence of HCV infection compared with the general population. Chronic HCV in those on dialysis and in kidney transplant recipients is associated with higher morbidity and mortality than uninfected patients. The HCV‐infected population is also at risk of developing extrahepatic manifestations associated with altered immune system function and chronic inflammation with cryoglobulinaemic vasculitis being the most common of these manifestations. Therefore, patients with CKD stages 4‐5 have to be considered priority patients for HCV therapy. New antiviral therapies have the potential to improve outcomes in this vulnerable patient population, including those on haemodialysis. Recently published studies conducted in kidney transplant recipients have demonstrated successful outcomes. It is thus essential that we carefully select the most appropriate DAA regimen and the best time for treatment in the context of kidney transplantation or cryoglobulinaemic vasculitis. While sofosbuvir, the only approved nucleotide NS5B inhibitor, has been the backbone of most pangenotypic therapeutic regimens, it has a limitation in those with advanced kidney disease. The currently approved regimens for those with stage 4/5 CKD, while effective, have challenges in that they apply to genotype 1/4 and may require RBV for genotype 1a. Globally, genotype 3 is a common infection, and thus, this group with CKD presents a huge unmet need for effective therapies. As therapy of HCV in renal transplant recipients has been highly successful, it provides an opportunity to expand the use of HCV‐infected organs in solid organ transplantation.     

How I manage patients with Fanconi anaemia

Fanconi Anaemia is a rare, genetic heterogeneous multisystem disease that is the most common congenital syndrome of marrow failure. Twenty genes have been reported to cause the disease. Remarkable progress has been made over the last 20 years in the understanding of the genetic and pathophysiological mechanisms. Unfortunately, these advances have not been completely paralleled by advances in medical treatment, where the most important component remains stem cell transplantation. This therapy, although contributing to long‐term negative effects, such as increased occurrence of late malignancies, is the only current option capable of prolonging the survival of patients. In spite of relevant recent progress in matched unrelated donor transplants, the largest studies with longer follow‐up still show a superiority of matched sibling donor transplants with a success rate, in selected cohorts, of over 90%. This article reviews different aspects of the disease, including genetics, diagnosis and treatment options, with special focus on stem cell transplantation, comprehensive post‐diagnosis management, decision‐making processes and long‐term follow‐up.     

Liver transplantation for severe alcoholic hepatitis–The CON view

In patients with severe alcoholic hepatitis (AH) who have failed medical therapy, liver transplantation (LT) remains a controversial therapeutic option. This is exemplified by the fact that most of these patients will not have had a period of abstinence prior to consideration for transplantation. Both abstinence before transplantation and the duration of abstinence are important predictors of post‐transplant relapse. Furthermore, relapse after transplantation has been associated with accelerated graft injury and increase mortality. Recent pilot studies have demonstrated a benefit in short‐term survival with early transplantation in highly selected small number of patients compared to matched controls. The results of these studies raises the possibility of extending graft allocation to these subjects. Despite stringent assessment and a multi‐tiered approach to selecting out patients for transplantation, the relapse rate was not insignificant at 12%. As the long‐term outcome remains unclear, further relapses with time can still occur. These studies also highlight the fact that the overwhelming majority of subjects with severe AH who are non‐responsive to medical therapy are not suitable for LT. Indeed, further large‐scale multicentre prospective studies with long‐term follow‐up are required to confirm the preliminary findings.     

Factors associated with nutritional status in liver transplant patients who survived the first year after transplantation

Background and Aims: Most studies published focus on the evaluation of the impact of nutritional status on the morbidity and mortality during the immediate postoperative period or on the short‐term evolution of liver transplant patients. The aim of the study was to evaluate long‐term trends in nutritional status. Methods: Seventy patients consecutively submitted to liver transplantation were studied. Nutritional assessment was performed the day before transplantation and the 45, 90, 180 and 365 days after transplantation, consisting of determination of dietary intake, anthropometric and biochemical analysis. Results: Sixty‐nine percent of the patients presented with malnutrition on the day before liver transplantation, decreasing to 44% at end of the first year. The prevalence of protein–calorie malnutrition (PCM) was 63% at 90 days post‐transplant. A significant difference of PCM was observed between patients with cirrhosis and non‐cirrhotic disease (53.6% × 100%) at 90 days post‐transplant. The pre‐transplant nutritional diagnosis and 90‐day calorie intake were identified as variables independently associated with nutritional status at 90 days post‐transplant. The variables independently associated with nutritional status in the 1‐year assessment were pre‐transplant PCM and 365‐day calorie requirements. Conclusion: No influence on nutritional status was observed for peri‐ or postoperative factors after 3 or 12 months of follow up. As expected, dietary factors, especially adequate calorie intake, were always associated with nutritional status during all periods analyzed.     

Successful multiple organ donation after donor brain death due to Actinomyces israelii meningitis

The increasing gap between availability of solid organs for transplantation and the demand has led to the inclusion of donor organs that, according to current guidelines, may be discarded, some of them because of the possibility for transmission of infection to the recipients. We present the first report, to the best of our knowledge, of a case of a brain‐dead donor with a localized and treated Actinomyces israelii central nervous system infection who, after a thorough evaluation, provided organs for successful transplant procedures in four recipients. There was no evidence of transmission of infection within a 6‐month follow‐up. Relative contraindications must be individualized in order to expand the number of real organ donors, emphasizing caution in rare causes for brain death in which patients should be thoroughly evaluated for possible donation.     

Treat chronic hepatitis C virus infection in decompensated cirrhosis – pre‐ or post‐liver transplantation? the ironic conundrum in the era of effective and well‐tolerated therapy

The management of hepatitis C virus (HCV) infection in patients with decompensated cirrhosis has evolved dramatically over the past few years mainly due to the availability of all‐oral antiviral regimens. The currently approved all‐oral direct‐acting antivirals (DAA) containing sofosbuvir, ledipasvir, daclatasvir and ribavirin, in various combinations, have shown to be safe and effective in patients with decompensated cirrhosis with sustained virological response (SVR) rates nearly comparable to those with well‐compensated liver disease. Unique issues yet remain such as the challenges with renal insufficiency, tolerability of ribavirin and risk of further hepatic decompensation with a protease inhibitor‐based regimen. While most patients who achieve SVR have demonstrated improvement in hepatic synthetic function over the short course of follow, the long‐term beneficial effects are unknown. Further, the baseline predictors of improvement in hepatic function have not been well delineated and thus have left us in a quandary as to what we might expect with successful therapy and thus we are at a loss to well educate our patients. The major concern, in potential liver transplant candidates, is of unintended ‘harm’ by achieving SVR but without improvement in hepatic function to an extent where the patients might function well. As HCV therapies are as effective in liver transplant recipients, there is a growing sentiment in some of the transplant quarters that those with decompensated liver disease and awaiting liver transplant be treated for HCV after liver transplant. This strategy would thus eliminate any concern of leaving a patient in ‘no person's’ land by treating HCV successfully pretransplant but not to the point of functional normalcy, while also would maintain the risk of HCC. Yet a contrarian view would be that not all patients have access to liver transplantation (LT), cannot bear the cost, have comorbidities or contraindications to LT. While the debate continues, it is essential that we develop robust predictors of improvement in liver function so that we can carefully select our patients for therapy in the context of liver transplantation.