Antiviral treatment in patients with hepatitis C virus-related cirrhosis awaiting liver transplantation

End stage liver disease due to hepatitis C virus (HCV) infection is the most common indication for liver transplantation (LT) worldwide. Regretfully, infection of the graft by HCV occurs almost universally after LT, causing chronic hepatitis and early progression to cirrhosis in a significant proportion of recipients. Moreover, graft and patient survival are significantly worse in patients undergoing LT for HCV-related cirrhosis than in those transplanted for other indications. Therefore, many LT centers consider antiviral treatment with interferon and ribavirin the mainstay of managing recurrent HCV disease in LT recipients. The optimal time to start treatment is unclear. In most instances, treatment is initiated when histological evidence of disease recurrence, either at protocol or on-demand liver biopsies, is observed after LT. However, antiviral treatment initiated before LT is a potential option for some patients for two reasons: first, clearing or suppressing HCV before LT may reduce or eliminate the risk of recurrent hepatitis C in the transplanted liver and thereby improve survival; second, clearing HCV in cirrhotic patient may halt disease progression and avoid the need for transplantation. In this article, the results obtained by pre-transplant antiviral regimens administered to HCV-positive cirrhotic patients awaiting LT are discussed

Risk factors for hepatocellular carcinoma recurrence after liver transplantation

Liver transplantation (LT) provides an excellent option for the long-term survival of patients with unresectable hepatocellular carcinoma (HCC) based on the Milan criteria. Despite careful selection of patients, HCC may still recur after LT, which represents the most important negative predictor of post-transplant survival. The growing demand for LT in HCC has led to the expansion of patient selection criteria, with a resultant increase in the risk of post-transplant HCC recurrence. Numerous tumor and host factors predict HCC recurrence. The morphological, histological, and serological characteristics of tumors in predicting HCC recurrence have been extensively studied. Furthermore, the type and duration of anticancer response before LT has also been considered a surrogate marker of tumor aggressiveness and is associated with the risk of recurrence. The demographic and clinical characteristics of recipients, as well as the type and duration of exposure to immunosuppressive therapy, represent the main host-related risk factors. Many studies have attempted to describe predictive models for the risk of HCC recurrence, considering evaluable parameters both before and after LT. Although many models have been proposed, relatively few have been externally validated on different patient populations. This paper aims to comprehensively summarize the available data on the predictive factors of HCC recurrence after LT, and to examine and discuss those that have been externally validated

Liver Transplantation in Patients with Hepatocellular Carcinoma beyond the Milan Criteria: A Comprehensive Review

The Milan criteria (MC) were developed more than 20 years ago and are still considered the benchmark for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). However, the strict application of MC might exclude some patients who may receive a clinical benefit of LT. Several expanded criteria have been proposed. Some of these consider pretransplant morphological and biological variables of the tumor, others consider post-LT variables such as the histology of the tumor, and others combine pre- and post-LT variables. More recently, the HCC response to locoregional treatments before transplantation emerged as a surrogate marker of the biological aggressiveness of the tumor to be used as a better selection criterion for LT in patients beyond the MC at presentation. This essential review aims to present the current data on the pretransplant selection criteria for LT in patients with HCC exceeding the MC at presentation based on morphological and histological characteristics of the tumor and to critically discuss those that have been validated in clinical practice. Moreover, the role of HCC biological markers and the tumor response to downstaging procedures as new tools for selecting patients with a tumor burden outside of the MC for LT is evaluated

An Essential Guide for Managing Post-Liver Transplant Patients: What Primary Care Physicians Should Know

With long-term survival after liver transplantation becoming the rule, care for medical problems arising over time in liver transplanted patients gained increasing importance. The most common causes of death occurring more than one year after liver transplantation are unrelated to liver diseases and facilitated by immunosuppressive treatments, such as malignancies, renal failure, cardiovascular, metabolic and infectious diseases. Recipients receive life-long follow-up care at transplant centers; however, the increasing number of liver transplanted patients is saturating the health care supply that transplant centers have to offer. Primary care physicians are increasingly exposed to liver transplanted patients even in the early periods after transplant and an understating of the most common risks and complications faced by these patients would enhance their care. This article reviews the long-term care of liver transplant recipients, emphasizing the key internal medicine-related issues that should be known by the primary care physicians. A specific section is devoted to implementing strategies to involve these physicians in the long-term follow-up of liver transplanted patients in close collaboration with transplant hepatologists

Recurrent and treatment-unresponsive spontaneous bacterial peritonitis worsens survival in decompensated liver cirrhosis

Background: Spontaneous bacterial peritonitis (SBP) remains a major complication of cirrhosis. However, the incidence and the real impact of SBP in determining patient survival rates remain unclear. This study aims to evaluate the incidence and risk factors for SBP development and the role of SBP in predicting transplant-free survival. Methods: Two hundred two consecutive patients underwent 492 paracenteses with biochemical and microbiological analysis of the ascitic fluid. When multiple paracenteses had been performed on a given patient, the first SBP-positive paracentesis or the first paracentesis conducted when none was diagnostic for SBP was included in the study. Results: SBP was detected in 28 of 202 (13.9%) patients; in 26 of 28 patients, the neutrophil count in the ascitic fluid was $250 cells/ml, and in 15 of 28 patients, the cultures were positive. Variables inde- pendently associated with SBP were as follows: a higher model of end-stage liver disease (MELD) score, the serum glucose value, elevated CRP serum levels, and higher potassium serum levels. Overall, the median (range) transplant-free survival was 289 (54\u20131253) days. One hundred (49.5%) patients died, whereas 35 patients (17.3%) underwent liver transplantation. Independent predictors of death or liver transplantation were a higher MELD score and the development of SBP, especially if it was antibiotic-resistant or recurrent SBP. Conclusion: The occurrence of SBP is associated with more severe liver dysfunction in conjunction with the presence of inflammation. Unlike the occurrence of SBP per se, failure of first-line antibiotic treatment and SBP recurrence appear to strongly influence the mortality rat

Low risk of nosocomial severe acute respiratory syndrome-coronavirus-2 infection in patients with liver disease admitted to a hepatology unit at an academic hospital: A single-center experience

Background: Patients with liver disease may be at increased risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection due to immune dysfunction. However, the risk of nosocomial SARS-CoV-2 infection in these patients remains unknown. This study aimed to determine whether patients with liver disease are at an increased risk of nosocomial transmission of SARS-CoV-2 infection upon admission to the hospital for diagnostic or therapeutic procedures. Methods: The study prospectively enrolled 143 patients who were admitted at least once to the hepatology unit at our hospital; 95 patients (66%) were admitted at least twice during the study period. History of past symptomatic SARS-CoV-2 exposure was assessed on the day before hospital admission via an interview. Patients were evaluated for active SARS-CoV-2 infection via real-time reverse transcription–polymerase chain reaction (RT-PCR) performed on nasopharyngeal swabs and tests for serum anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. Results: None of the patients enrolled tested positive for SARS-CoV-2 infection by RT-PCR at the first or the second clinical evaluation. One patient who had previously received a liver transplant and who had a history of symptomatic SARS-CoV-2 infection that occurred 4 months before hospital admission tested positive for anti-SARS-CoV-2 IgG but not IgM antibodies at each of the two hospital admissions. Conclusions: The results of our study suggest that patients with liver disease are at no increased risk of nosocomial SARS-CoV-2 infection. These data support the policy of maintaining clinical hospital checks that will be necessary until or possibly even after the completion of the current SARS-CoV-2 vaccination campaign

Vitamin D and the risk of acute allograft rejection following human liver transplantation.

BACKGROUND: Vitamin D may act as an immune modulator in experimental and human organ transplantation, but these data are yet to be confirmed in human liver transplantation (LT). AIM: This study aimed to assess the relationship between acute liver allograft cellular rejection (ACR) and pretransplant serum vitamin D concentration or post-transplant vitamin D supplementation. METHOD: We studied 133 LT recipients who underwent two per protocol allograft biopsies in the early post-operative period, plus on-demand biopsies as clinically indicated. ACR estimate was given according to the Banff scheme in biopsies obtained along two follow-up periods: (a) from the transplant operation to the end of the second month (0-2 months); (b) and from the third month to the end of the eighth month (3-8 months) post-LT. RESULTS: The median pretransplant serum 25-hydroxyvitamin D concentration was 12.5 ng/ml; 40 patients had concentrations < or =12.5 ng/ml, of whom six had < or =5.0 ng/ml. Seventy-nine recipients received oral vitamin D(3) supplementation to treat post-transplant osteoporosis. In the 0-2 months period, moderate-to-severe rejection episodes were independently associated with cytomegalovirus reactivation (P<0.005) and progressively lower pretransplant serum 25-hydroxyvitamin D concentrations (P<0.02). Early vitamin D(3) supplementation was independently associated with a lack of ACR (P<0.05). CONCLUSIONS: These results suggest that vitamin D may favour immune tolerance towards the liver allograft

Interleukin 6 promoter polymorphisms influence the outcome of chronic hepatitis C.

Host genetic variation may affect the outcome of chronic viral hepatitides, favoring viral clearance and/or modulating the inflammatory response to persistent infection. Our aims were to assess whether interleukin 6 (IL-6) promoter polymorphisms are associated with chronic hepatitis C virus (HCV) infection and to clarify the role of IL-6 haplotypes in facilitating progressive disease. The study included 424 Italian patients (233 males, median age 53 years) affected by HCV chronic infection. IL6 -1363, -597, -572, -174, and +2954 polymorphic loci were assayed by means of restriction fragment length polymorphism. Three hundred forty-four healthy Italian blood donors (245 males, median age 50 years) served as controls. Comparing patients and controls analysis of molecular variance was highly significant (p\u2009<\u20090.0001); at a locus by locus approach, the frequencies of minor alleles in the -1363 (p\u2009<\u20090.02), -597 (p\u2009<\u20090.02), and -174 (p\u2009<\u20090.01) polymorphisms were confirmed to be less represented in patients than in controls. Carrying the wild-type G allele at the -597 and -174 loci identified an unfavorable haplotype; carrying the minor allele in one/both loci identified an indifferent/favorable haplotype. Male patients carrying two unfavorable haplotypes had the highest adjusted mean\u2009\ub1\u2009standard error Ishak staging score (3.56\u2009\ub1\u20090.19), while females carrying one or no unfavorable haplotypes had the lowest (2.69\u2009\ub1\u20090.21); the remaining patients had an intermediate value (3.12\u2009\ub1\u20090.13, p\u2009<\u20090.01). In conclusion, IL-6 promoter polymorphisms influence the development of chronic HCV infection. With the permissive effect of male gender, haplotypes represented by the wild-type allele for -597 and -174 loci appear to favor a worse evolution of the disease

OCCULT HEPATITIS B VIRUS INFECTION IN LIVER TRANSPLANT RECIPIENTS WITH RECURRENT HEPATITIS C: RELATIONSHIP WITH DONOR AGE AND FIBROSIS PROGRESSION

Liver transplantation (OLT) recipients who receive a graft from donors positive for hepatitis B virus (HBV) anti-core antibodies may develop overt "de novo" HBV infection. The study was undertaken to explore how often HBV infection may remain occult after OLT for hepatitis C, and whether it may represent a factor of graft fibrosis progression. We studied 30 consecutive patients transplanted for hepatitis C liver disease. Specimens from the native liver and from the graft were searched for occult HBV infection (O-HBV). In the native liver, 8/30 patients had detectable O-HBV; during the follow-up, O-HBV infection was demonstrated in 14 graft specimens. Graft O-HBV was associated with older donor age (> or =50 yr; 8/9 vs. 6/21, p 40 yr had faster fibrosis progression than recipients with no post-transplant O-HBV, whose grafts came from donors aged >40 yr and recipients whose grafts came from donors aged < or =40 yr (4/7 vs. 1/7 vs. 2/16, p < 0.05). In OLT recipients, O-HBV is more likely to occur when grafts are obtained from aged donors and may affect the rate of fibrosis progression because of recurrent hepatitis C