Liver transplantation in hepatitis C virus-related cirrhosis

End-stage liver disease associated with HCV infection has become one of the leading indications for liver transplantation and it is the most common disease recurring after liver transplantation. The aim of this retrospective study was to asses factors potentially affecting outcome in patients transplanted for HCV-related liver disease. Among 164 adult patients who underwent orthotopic liver transplantation from December 1994 to December 2002, 134 survived >2 months, including 25 with HCV-related liver disease. Mean follow-up after LTx was 24.8 months (range, 2.1-99.4). Anti-HCV was negative in all donors. The parameters considered in our analysis were: the course, outcome, and liver function tests at 1-year follow-up after HCV reinfection: the potential impact of maintenance and induction immunosuppressive regimens; and episodes of acute rejection. Deterioration of graft function because of HCV reinfection occurred in 16 patients (64%). Mean time for deterioration of liver function related to reinfection was 4.5 months (range, 0.83-23). Induction and maintenance immunosuppression did not affect outcome of HCV-infected liver transplant recipients. Aminotransferases were significantly higher among HCV-infected recipients than among the other patients in our series. There was a slight tendency for earlier recurrence of HCV hepatitis among patients treated with high-dose steroids because of acute rejection.     

Blood eosinophilia after living donor liver transplantation for hepatitis C virus-related cirrhosis

BACKGROUND: Differentiating between acute cellular rejection (ACR) and recurrent hepatitis C virus after liver transplantation in hepatitis C virus-positive patients is difficult, but vital for preventing graft loss. METHODS: The blood eosinophil counts 3 days before or on the day of biopsy were retrospectively reviewed to evaluate their value for predicting ACR in 91 biopsy samples from 45 patients. RESULTS: Eosinophil counts on the day of biopsy were significantly higher in the ACR group (n = 20) than in the non-ACR (n = 71) group, although the difference was negligible 3 days before the biopsy. A relative eosinophil count of 2% or an absolute eosinophil count of 200 cells/mm(3) predicted ACR with a specificity of 94% or 96%, respectively. CONCLUSIONS: Blood eosinophil count on the day of biopsy can be helpful in the diagnosis of ACR in patients who underwent living donor liver transplantation for hepatitis C virus-related cirrhosis.     

Hepatitis C virus-related fibrosing cholestatic hepatitis after cardiac transplantation: is azathioprine a contributory factor?

We report a patient who acquired hepatitis C virus (HCV) infection at cardiac transplantation, developing fibrosing cholestatic hepatitis (FCH) with early liver failure and a fatal outcome. FCH is a recently described clinicopathological entity characterized by a cholestatic pattern of serum liver enzyme abnormalities, a progressive course leading to liver failure, and a pathological picture defined by periportal fibrosis, neutrophilic infiltrates and signs of histological cholestasis. Although it was initially described secondary to hepatitis B virus infection, it has also been recently related to HCV infection. Some histopathological features consistent with azathioprine hepatotoxicity like cholestasis, perisinusoidal fibrosis, veno-subocclusive lesions and nodular regenerative hyperplasia were also observed in this case. Therefore, a direct cytopathic effect of HCV and the concurrent pathogenic role of azathioprine hepatotoxicity may be involved in the development of this complication of transplantation.     

Hepatitis C virus (HCV)-related cryoglobulinemia after liver transplantation for HCV cirrhosis

The aim of this study was to analyze the clinical impact of hepatitis C virus (HCV)-related cryoglobulinemia in patients that had received liver transplants after HCV cirrhosis. Thirty patients who had received transplants between 1990 and 1996 for HCV cirrhosis and who had a follow-up longer than 1 year were studied. Serum HCV RNA levels, HCV genotype, cryoglobulinemia, rheumatoid factor, serum C3 and C4, IgA, IgG, IgM levels, liver tests, and liver histology were studied 30 +/- 16 months post-transplant. Cryoglobulinemia was found in 9 of 30 patients (30.0%) and was symptomatic in 4 of the 9 cases (glomerulonephritis, 1 case; palpable purpura, 3 cases). Age, sex distribution, alanine aminotransferase (ALAT) activity, and Knodell score did not differ, whether cryoglobulinemia was present or not. Rheumatoid factor (209.5 +/- 70.4 IU/l vs 12.0 +/- 4.4 IU/l, P = 0.004) and IgM levels (3.2 +/- 0.5 g/l vs 1.6 +/- 0.9 g/l, P = 0.0001) were significantly higher, and C4 levels (0.16 +/- 0.16 g/l vs 0.30 +/- 0.10 g/l, P = 0.009) were significantly lower in patients with cryoglobulinemia. One patient died from cryoglobulin-related renal failure. We concluded that, after liver transplantation (LT) for HCV cirrhosis, cryoglobulinemia was frequent and often symptomatic. Cryoglobulinemia did not seem to be associated with more severe graft damage. Cryoglobulinemia-associated morbidity must be taken into account in the management of post-transplant HCV infection.     

Treatment of a patient with hemophilia A and hepatitis C virus-related cirrhosis by living-related liver transplantation from an obligate carrier donor

BACKGROUND: Decompensated hepatitis C virus (HCV)-related cirrhosis is the main indication for liver transplantation. We report the first successful living-related liver transplantation in a 49-year-old hemophilia A patient with end-stage HCV-related cirrhosis using a graft obtained from his 20-year-old daughter, an obligate carrier. METHODS: The donor's autologous fresh-frozen plasma rich in factor VIII (FVIII) by treatment with 1-deamino-8-D-arginine vasopressin was prepared before the operation. At induction, 1-deamino-8-D-arginine vasopressin was given to the donor to increase plasma FVIII level. In addition, autologous fresh-frozen plasma containing high FVIII concentrate was infused intraoperatively. The right lobe was harvested from the donor and transplanted orthotopically. The recipient was treated postoperatively with recombinant FVIII and immunosuppressive agents. RESULTS: The donor did not receive recombinant FVIII or allogenic blood during perioperative periods. No bleeding was encountered in the donor perioperatively. The recipient showed a steady increase in FVIII activity postoperatively and was discharged 40 days after transplantation. Ribavirin and interferon-alpha were provided for 3 months postoperatively to prevent potential recurrence of HCV infection. Serum HCV-RNA by RT-PCR became negative after such treatment. CONCLUSIONS: End-stage liver disease in patients with hemophilia A can be an indication for living-related liver transplantation. Furthermore, a graft from a living-related donor with hemophilia A carrier seems to be suitable provided such individuals receive adequate support for coagulopathies.     

Hepatitis B and hepatitis C viruses in liver transplantation

Liver transplantation (LT) for end-stage liver disease (ESLD) secondary to hepatitis viruses has evolved rapidly during the last two decades. ESLD secondary to hepatitis C virus (HCV) accounts for approximately 50% of LT in the United States and Europe. Despite the decrease in the number of new HCV infections, the prevalence of advanced HCV-related liver disease is steadily increasing. In light of the near universal recurrence of posttransplantation HCV infection and our limited ability to treat recurrent disease, transplantation is in danger of being overrun by viral hepatitis, unless effective strategies can be used to treat disease, expand the donor pool of available organs, and prevent disease recurrence.In the early 1980s, results of LT for chronic hepatitis B virus infection were hampered by recurrent infection and subsequent allograft failure. However, with the introduction of passive immunoprophylaxis with hepatitis B immunoglobulin and treatment with potent nucleoside analogs, there has been a resurgence of LT for hepatitis B virus-related ESLD.Despite the wide acceptance of LT as a therapy for ESLD, there is little consensus on the appropriate immunosuppressive regimens, and prophylactic and therapeutic treatments vary widely from one center to another. This review summarizes available data and highlights appropriate strategies to improve outcomes.     

Hepatitis C virus infection as a possible risk factor for ductopenic rejection (vanishing bile duct syndrome) after liver transplantation

Irreversible ductopenic rejection (DR) after orthotopic liver transplantation (OLT) is a major cause of late hepatic allograft failure. A variety of risk factors for DR have been postulated, but they are controversial. All transplant recipients at our institution with graft survival of more than 1 month (n=120) were examined retrospectively with a view to possible risk factors for DR. These factors included age, sex, underlying liver disease, hepatitis B and C infections, donor-recipient CMV status, post-OLT CMV infections, immunosuppressive regimen, ABO blood type, and HLA class I and class II mismatches. Statistical analysis was performed with the univariate chisquare test or the two-tailed Fischer's exact test. Ten patients (8.3%) developed DR. Seventeen patients had HCV infections after OLT. In this group, the incidence of DR was highest (4 of 17, or 23.5%). This was significantly higher than for all other OLT groups (6 of 103 patients, or 5.8%; P<0.03). The other factors analyzed did not reach statistical significance, including those that other authors found important for the development of DR. It may well be that hepatitis C infection predisposes one to the development of DR after OLT.     

Increased mortality after liver transplantation for hepatocellular carcinoma in hepatitis B-associated cirrhosis

Transplant patients suffering from hepatocellular carcinoma in cirrhosis are selected according to tumor nodule number and diameter. Vascular invasion and histopathological grading are predictive of outcome. The prognostic influence of hepatitis B-cirrhosis has been investigated after resection and after local tumor treatment, but not after transplantation. Of the 1,188 transplantations performed between 1989 and 2000, 120 were on patients with hepatocellular carcinoma in cirrhosis (HCC) (follow-up: 57 months; 1-140 months). Within this group, 25 patients (21%) suffered from hepatitis B. Pre-transplant selection criteria were a maximum diameter of 5 degrees cm in uni-nodular tumors, or 3 degrees cm for two to three tumor nodules. The rate of tumors with 2-3 tumor nodules was increased in the hepatitis-B group (52% vs. 29%; P<0.05). Other tumor characteristics did not differ. In the hepatitis-B group, more patients died post-transplantation (44% vs.22%; P<0.05). This difference was due to unspecific causes, not to tumor recurrence or re-infection. These findings may be indicative of a more complicated course in patients suffering from hepatitis B in general.     

Hyponatremia a valuable predictor of early mortality in patients with cirrhosis listed for liver transplantation

The current policy for organ allocation in liver transplantation is to give priority to the sickest patients mostly using model for end-stage liver disease (MELD) score in ranking. However, other factors as serum sodium may be of value in predicting early mortality. In this single-center study, patients with cirrhosis over age 14 on the liver transplant wait-list from September 1998 to June 2007 were followed for six months from the time of listing to evaluate the value of hyponatremia on mortality. Of 612 listed patients, 51 were transplanted who were excluded from survival analysis and 55 died without transplantation within the first three months. The numbers of transplanted and dead patients during months 3-6 were 29 and 24, respectively. Both MELD score and serum sodium at the time of listing were independent predictors of early mortality. On bivariate analysis, serum sodium of <130 mEq/L beside MELD was a significant predictor of mortality within 90 and 180 d. Serum sodium level <135 mEq/L masked the difference in mortality between patients with refractory and non-refractory ascites. Serum sodium level of <130 mEq/L and an increased MELD score are significant predictors of early mortality in patients listed for liver transplantation.     

Transjugular intrahepatic portosystemic shunt for hepatitis C virus-related portal hypertension after liver transplantation

Ghinolfi D, De Simone P, Catalano G, Petruccelli S, Coletti L, Carrai P, Marti J, Tincani G, Cicorelli A, Cioni R, Filipponi F. Transjugular intrahepatic portosystemic shunt for hepatitis C virus‐related portal hypertension after liver transplantation. Abstract: This is a single center retrospective review of 19 consecutive liver transplant (LT) patients with hepatitis C virus (HCV)‐related graft recurrent hepatitis who underwent transjugular intrahepatic portosystemic shunt (TIPS) at a median interval of 21 months (range: 5–50) from LT. Indications were refractory ascites in 11 patients (57.9%), hydrothorax in six (31.6%), and both in two (10.5%). TIPS was successful in 94.7% of cases (18/19) with only one procedure‐related mortality (5.3%) owing to sepsis on day 35. At a median follow‐up of 23 months (range: one month–nine yr), TIPS allowed for symptoms resolution in 16 patients (84.2%), with ascites resolving in all cases and hydrothorax persisting in 2. Post‐TIPS patient survival at six months, one yr, and three yr was 84.2%, 73.7%, and 56.8%, respectively. We compared these results with a control group of 29 patients with HCV recurrence but without unresponsive ascites or hydrothorax. Patients in the control group had better survival than patients undergoing TIPS placement. However, survival of TIPS patients with a MELD score lower than or equal to 12 was similar to that of the control group. We conclude that TIPS may be used to treat complications secondary to HCV.     

Double primary liver cancer (intrahepatic cholangiocarcinoma and hepatocellular carcinoma) in a patient with hepatitis C virus-related cirrhosis

We herein report a rare case of double primary liver cancer, consisting of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). A 67-year-old Japanese man with hepatitis C virus-related liver cirrhosis was diagnosed with multiple HCC in S7 and S8 of the liver. We performed a hepatic resection of S7 and S8. The liver tumors in S7 and S8 were pathologically diagnosed as HCC and ICC, respectively. Multiple recurrence of the HCC found 7 years after the surgery was successfully treated with transcatheter arterial chemoembolization. Subsequently, this patient has been doing well, without HCC recurrence. Double primary liver cancer is very rare, and only 21 resected cases have been reported, including that in our patient. We reviewed at all cases in the Japanese- and English-language literature to investigate the clinicopathological features. Our literature review revealed that the present patient is the longest survivor among patients who have undergone hepatectomy for double primary liver cancer.     

Hepatitis C in liver transplantation: preliminary study of prognostic factors

Abstract At the University of Miami liver transplantation for chronic liver disease in HCV-positive patients has shown good results, with a 92% patients survival rate (follow up 8 to 57 months, median 21). None the less, we found that a large number of patients are expected to develop serious histological graft damage and may need retransplantation, which may place a further strain on the already scarce donor resources. We have conducted a preliminary investigation on the importance of parameters which may correlate with the prognosis of HCV grafts. We found no impact of HLA match or typing. An interesting hypothesis, which deserves further investigation, is that some HCV strains could be more virulent than others and play a role as an independent risk factor. We have identified six strains among our patients and the BK serotype shows a trend to be associated with a worse outcome. We have found that patients developing and maintaining higher liver enzyme levels (ALT and GGT) after transplant and those with higher levels of viremia may be at risk to develop serious damage to their grafts.     

Off-pump coronary artery bypass grafting in a patient with Child class C liver cirrhosis awaiting liver transplantation

We report the case of a Child class C cirrhotic patient who was diagnosed with coronary artery disease in the course of his pretransplantation evaluation. He underwent off-pump coronary artery bypass grafting (OPCAB), which was complicated with acute renal failure. The morbidity and mortality associated with cardiac operation in patients with cirrhosis is discussed, and the potential advantage of OPCAB in this patient population is emphasized.     

Laparoscopic liver resection for hepatitis B and C virus-related hepatocellular carcinoma in patients with Child B or C cirrhosis

Background

The aim of this study was to evaluate the clinical and oncological outcomes after laparoscopic liver resection (LLR) in patients with hepatitis B and C virus-related hepatocellular carcinoma (HCC) with Child B or C cirrhosis.

Methods

Between January 2004 and December 2013, LLR was performed in 232 patients with HCC. Of these, 141 patients also had pathologically proven cirrhosis. Sixteen patients with hepatitis B and C virus-related HCC with Child B or C cirrhosis were included in the study. Thirteen (81.3%) patients had Child B disease and three (18.8%) patients had Child C disease.

Results

The median operation time was 215 min, the median estimated blood loss was 350 mL, and the median hospital stay was eight days. Three patients (18.8%) experienced complications after surgery. There was no postoperative mortality or reoperation. The mean follow-up period was 51.6 months. HCC recurred in eight (50%) patients: seven intrahepatic recurrences and one extrahepatic recurrence. The treatments for recurrence were laparoscopic reoperation in one (6.3%) patient, trans-catheter arterial chemo-embolization (TACE) in one (6.3%) patient, radiofrequency ablation (RFA) in one (6.3%) patient, and combined TACE and RFA in four (25%) patients. The five-year postoperative overall survival (OS) and disease-free survival (DFS) were 84.4% and 41.7%, respectively.

Conclusions

This study demonstrates that LLR can be safely used in patients with hepatitis B and C virus-related HCC and Child B or C cirrhosis, with acceptable survival outcomes.     

Hepatitis C: a challenge to hepatologists and to the liver transplantation team

Hepatitis C is the main cause of cirrhosis and hepatocellular carcinoma and the leading indication of liver transplantation. The aim of this article was to review specific epidemiological, clinical and therapeutic aspects of hepatitis C and their implication for the hepatologists belonging to liver transplantation services. These specific aspects were reviewed in the literature mainly using Medline. Data regarding the epidemiological, clinical and therapeutic aspects of hepatitis C are discussed, with emphasis on their consequences for the liver transplantation team. Hepatitis C is a challenge for hepatologists and for the liver transplantation team. The burden we observe today is the late consequence of infection that occurred in the past. Measures for early recognition of complications of liver disease are recommended. HCV treatment should always be performed before liver transplantation if possible, but if not, HCV recurrence should be recognized and treated early after transplantation.     

Hepatitis C is a risk factor for death after liver retransplantation.

Retransplantation for liver allograft failure associated with hepatitis C virus (HCV) has been increasing due to nearly universal posttransplant HCV recurrence and has been demonstrated to be associated with poor outcomes. We report on the risk factors for death after retransplantation among liver recipients with HCV. A retrospective cohort of liver transplant recipients who underwent retransplantation between January 1997 and December 2002 was identified in the Scientific Registry of Transplant Recipients database. Cox regression was used to assess the relative effect of HCV diagnosis on mortality risk after retransplantation and was adjusted for multiple covariates. Of 1,718 liver retransplantations during the study period, 464 (27%) were associated with a diagnosis of HCV infection. Based on Cox regression, retransplant recipients with HCV had a 30% higher covariate-adjusted mortality risk than those without HCV diagnosis (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.54; P = 0.002). Other covariates associated with significant relative risk of death after retransplantation included older recipient age, presence in an intensive care unit (ICU), serum creatinine, and donor age. Additional regression analysis revealed that the increase in mortality risk associated with HCV was concentrated between 3 and 24 months postretransplantation, among patients age 18 to 39 at retransplant, and in patients retransplanted during the years 2000 to 2002. In conclusion, HCV liver recipients account for a considerable proportion of all retransplantations performed. Surprisingly, younger age predicted a higher mortality for recipients with HCV undergoing liver retransplantation. This may reflect a willingness to retransplant younger patients with an increased severity of illness or a more virulent HCV infection in this population. Although HCV was predictive of an increased risk of death, consideration of other characteristics of HCV patients, including donor and recipient age and need for preoperative ICU care may identify those at significantly higher risk.