Well-compensated Cirrhosis Research Articles

Altered blood microbiome in patients with HCV-related Child-Pugh class B cirrhosis

BackgroundAltered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis). MethodsWe conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis. ResultsPatients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001). ConclusionsBlood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A.

Microwave Ablation in the Thermal Treatment of Hepactocellular Carcinoma: Case Report

Hepatocellular carcinoma (HCC) stands as one of the most prevalent malignant tumors [1], and is the cause of over one million deaths annually worldwide [2]. While surgical resection remains the preferred treatment for early-stage hepatocellular carcinoma (HCC) in well-compensated cirrhosis patients, thermal ablation techniques offer a credible non-surgical option. Their minimal invasiveness, high tolerability, safety, established efficacy in local disease control, virtually unlimited repeatability, and cost-effectiveness render them valuable alternatives. Microwave ablation (MWA) of HCC appears to be a safe and effective treatment. Here we report a case of 53-year-old male, followed for hepatitis C complicated by compensated cirrhosis, During the follow up, Laboratory tests found liver function tests were eleveted, α-fetoprotein (AFP) was normal. Abdominal ultrasound showed a focal hepatic mass straddling segments VI and VIII, rounded, well-limited, with heterogeneous hyperechoic echostructure, and splenomegaly. Contrast-enhanced abdominal computed tomography showed a chronic liver desease with a focal lesion straddling segments VI and VIII, oval, tissue-like, hypodense in the center, measuring 50x41mm, with signs of early arterial enhancement consistent with HCC characteristics and signs of portal hypertension and a multicystic kidney. Hepatic MRI revealed a chronic liver disease straddling segments VII and VIII of a hepatic lesion measuring 23x 22mm classified as Li-RADS 4 with signs of portal hypertension and splenomegaly. Based on these results, the patient was diagnosed as HCC with well compensated cirrhosis, and in view of the fact that he had only a single lesion and was in functional grade A of Child-Pugh classification and staged as BCLC-A in the Barcelona Clinic Liver Cancer (BCLC) staging system, the patient benefited from microwave ablation for his HCC, with good clinical, biological and radiological evolution. Microwave Ablation (MWA) emerges ..........

Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) associated with steatosis, hepatocellular injury, inflammation and fibrosis. In a Phase 2 trial in adults with NASH (NCT02912260), resmetirom, an orally administered, liver-targeted thyroid hormone receptor-β selective agonist, significantly reduced hepatic fat (via imaging) and resolved NASH without worsening fibrosis (via liver biopsy) in a significant number of patients compared with placebo. To present the design of the Phase 3 MAESTRO clinical programme evaluating resmetirom for treatment of NASH (MAESTRO-NAFLD-1 [NCT04197479], MAESTRO-NAFLD-OLE [NCT04951219], MAESTRO-NASH [NCT03900429], MAESTRO-NASH-OUTCOMES [NCT05500222]). MAESTRO-NASH is a pivotal serial biopsy trial in up to 2000 adults with biopsy-confirmed at-risk NASH. Patients are randomised to a once-daily oral placebo, 80 mg resmetirom, or 100 mg resmetirom. Liver biopsies are conducted at screening, week 52 and month 54. MAESTRO-NAFLD-1 is a 52-week safety trial in ~1400 adults with NAFLD/presumed NASH (based on non-invasive testing); ~700 patients from MAESTRO-NAFLD-1 are enrolled in MAESTRO-NAFLD-OLE, a 52-week active treatment extension to further evaluate safety. MAESTRO-NASH-OUTCOMES is enrolling 700 adults with well-compensated NASH cirrhosis to evaluate the potential for resmetirom to slow progression to hepatic decompensation events. Non-invasive tests (biomarkers, imaging) are assessed longitudinally throughout, in addition to validated patient-reported outcomes. The MAESTRO clinical programme was designed in conjunction with regulatory authorities to support approval of resmetirom for treatment of NASH. The surrogate endpoints, based on week 52 liver biopsy, serum biomarkers and imaging, are confirmed by long-term clinical liver-related outcomes in MAESTRO-NASH (month 54) and MAESTRO-NASH-OUTCOMES (time to event).

Immunotherapy for hepatocellular carcinoma in liver transplant patients (Literature review)

Hepatocellular carcinoma (HCC) is the third cause of cancer-related mortality worldwide, accounting for more than 800,000 deaths annually. Surgical removal of the neoplasm remains the most effective treatment option. Partial liver resection is an adequate solution for patients without cirrhosis or with well-compensated cirrhosis, orthotopic liver transplantation is necessary in patients with early stage HCC on the background of cirrhosis. Tumor recurrence remains a major limitation of long-term survival of patients after liver transplantation. Posttransplant immunosuppression reduces the body's antitumor defense, which is provided by natural immunity. This contributes to the development and progression of the tumor process. Purpose of the study: to analyze domestic and foreign publications that present treatment options for HCC recurrence after liver transplantation. Literature sources were searched in PubMed, Scopus, Web of Science, MEDLINE, eLibrary databases. The search was conducted in Russian and English by keywords: hepatocellular carcinoma, tyrosine kinase inhibitors, immune checkpoint inhibitors, therapy of HCC relapse, orthotopic liver transplantation, RETREAT index, regorafenib, nivolumab. The authors presented a review of the data on the use of tyrosine kinase inhibitors and immune checkpoint inhibitors to prevent HCC recurrence. The results of the analysis of literature sources showed that the issue of post-transplant immunosuppression is relevant. The large number of studies and clinical case reviews leaves hope that an effective way of immunosuppression for recurrent HCC patients after liver transplantation will soon be found.

Bariatric Surgery is Effective and Safe for Obese Patients with Compensated Cirrhosis: A Systematic Review and Meta-Analysis.

With the global pandemic of obesity and nonalcoholic fatty liver disease (NAFLD), the incidence of cirrhosis associated with nonalcoholic steatohepatitis (NASH) has greatly increased. This study aimed to evaluate the efficacy and safety of bariatric surgery in obese cirrhotic patients. PubMed, EMBASE, and the Cochrane Library were searched for relevant studies. Effectiveness outcomes were weight loss, remission of comorbidities, and improvement in liver function. Safety outcomes were procedural complications and mortality. A total of 15 studies were included in this meta-analysis. Patients with compensated cirrhosis lost weight significantly after surgery, and the percentage of excess weight loss was 60.44 (95% CI, 44.34 to 76.55). Bariatric surgery resulted in remission of NAFLD in 57.9% (95% CI, 27.5% to 88.3%), T2DM in 58.4% (95% CI, 48.4% to 68.4%), hypertension in 53.1% (95% CI, 43% to 63.3%), dyslipidemia in 59.8% (95% CI, 41.1% to 78.5%) of patients with cirrhosis. Bariatric surgery reduced the levels of alanine aminotransferase and aspartate aminotransferase. The incidence of surgical complications in patients with cirrhosis was about 19.2% (95% CI, 11.7% to 26.6%), which was higher than that in patients without cirrhosis (OR 2.67 [95% CI, 1.26 to 5.67]). Patients with cirrhosis had an overall mortality rate of 1.3%, and the mortality rates for compensated cirrhosis and decompensated cirrhosis were 0.9% and 18.2%, respectively. Bariatric surgery is effective for weight loss, remission of comorbidities, and reversal of liver damage. Although cirrhotic patients have a higher risk of complications and death, bariatric surgery is relatively safe for well-compensated cirrhosis.

Sofosbuvir-based therapies in genotype 2 hepatitis C virus cirrhosis: A real-life experience with focus on ribavirin dose.

This study aimed to investigate the efficacy and safety of sofosbuvir‐based therapies for the treatment of cirrhosis from hepatitis C virus (HCV) genotype 2 infection. Data of all consecutive HCV genotype 2 cirrhotic patients who started sofosbuvir‐based treatments between January 2015 and March 2017 in eight Italian tertiary hospitals were collected retrospectively. Overall, 273 patients (Child A: 94.5%) were enrolled. In the 194 subjects treated with sofosbuvir/ribavirin, median initial ribavirin dosage was 13.9 mg/kg/day, and therapy duration was 16 weeks. Sustained virological response (SVR) rates were 93.8% in intention‐to‐treat (ITT) and 95.3% in per‐protocol (PP) analyses for the 129 treatment‐naïve patients, and 96.9% (ITT) and 98.4% (PP) for the 65 treatment‐experienced subjects. Adverse events were reported in 142 patients (73.2%), but only 1.5% discontinued treatment. Eighty‐eight subjects with treatment‐induced anemia (mild: 34.5%, moderate: 7.7%, severe: 3.1%) had to reduce ribavirin dosage, but SVR rates were comparable to the weight‐based dose group, both in ITT (95.4% and 94.3%) and PP (97.7% and 95.2%) analyses, respectively. Moreover, ITT and PP SVR rates were similar between shorter (<20 weeks) (94.1% and 96.0%, respectively) and prolonged (≥20 weeks) regimens (95.7% and 96.7%, respectively). SVR rates in the 79 subjects treated with sofosbuvir/daclatasvir (without ribavirin) were similar (ITT: 96.2%; PP: 97.4%, respectively), without de novo/worsening anemia. In conclusion, in a real‐life study centered on genotype 2 patients with well‐compensated cirrhosis, sofosbuvir‐based regimens were associated with good SVR and tolerability rates, regardless of previous antiviral treatments, without a significant impact of on treatment ribavirin dose reductions.

Laparoscopic right posterior sectionectomy for HCC in cirrhotic liver: ICG for tumor enhancement and negative counter-staining of the transection plane

Background: The importance of anatomical reactions in liver cancer surgery is well known since the first description by Makuuchi in 1985, but its technical difficulty is equally known because of the absence of a clear demarcation of the hepatic segments during parenchymal transection. Takasaki et al. proposed a new concept of anatomical resection in which the Glissonean pedicles can be transected extrahepatically to identify the boundaries of the intersegmental planes. Based on these concepts, intraoperative Indocyanine-Green (ICG) fluorescence can be used to obtain a positive or negative staining of the segments to be resected. Methods: A 54-year-old male patient with well-compensated HCV-related cirrhosis underwent right posterior sectionectomy for a large HCC. 96h before surgery he was injected with 0.5 mg / kg of ICG to achieve intraoperative tumor enhancement. Surgical procedure starts with the preparation of the Pringle maneuver and the mobilization of the right liver. Then, to perform a formal anatomical resection with the so called Glissonean approach, we started the parenchymal dissection at the level of the De Rouvière sulcus, which allows to identify and isolate the portal branch of the right lateral posterior sector. This is then ligated with hemolocks and sectioned. Then 0,05 mg/kg of ICG were intravenously administrated. Results: A negative counter-staining of the transection plane for the right posterior sectionectomy was visualized. The sharp contrast between the dark area (segment 6-7) and the area highlighted in fluorescent green guided the parenchymal transection, allowing to obtain a true anatomical resection. Furthermore, a final check of the transection line was performed, and it turned out to be wrong in the lower portion, where the parenchymotomy was initially carried out without the use of indocyanine green fluorescence guidance. In this way, a re-assessing and a correction of the section line was carried out. Conclusions: The quality of the surgical act has greatly benefited from the use of ICG fluorescence, allowing to obtain a better visualization of the cancerous lesion, best resection margins, better quality specimen. The use of ICG can facilitate a technically complex procedure, through a visual immediacy that gives a real-time feedback on the goodness of the procedure, even allowing to correct a wrong transection plance and making the surgery more didactic.

Annals for Educators - 1 September 2020.

Annals for Educators - 1 September 2020.

Rates of Bleeding and Discontinuation of Direct Oral Anticoagulants in Patients With Decompensated Cirrhosis

Studies of the effects of direct oral anticoagulants (DOACs) in patients with cirrhosis have been limited by their small sample size, inclusion of patients with well-compensated cirrhosis, short follow-up times, inadequate validation of cirrhosis diagnoses, and non-standard definitions of bleeding. We aimed to systematically determine the characteristics, indications, and outcomes of patients with cirrhosis of all severity classes who received DOACs. We performed a retrospective study of 138 patients with confirmed cirrhosis (93 with Child-Turcotte-Pugh scores of B or C) at a single center who started DOAC therapy (58,984 person-days; median, 181 days per patient) from September 2011 through April 2019. We collected data on clinical characteristics, indications for DOAC use, and outcomes. Standardized and validated definitions for bleeding complications were used. Twenty-nine patients (21%) stopped therapy due to a diagnosis of or perceived bleeding. The most common bleeding events were non-variceal upper and lower intestinal bleeding. No pretreatment laboratory parameters were associated with bleeding while patients received treatment, including platelet count (P = .50), international normalized ratio (P = .34), creatinine (P = .27), and model for end-stage liver disease score (P = .22). Frequency of bleeding events related to DOAC did not differ significantly among patients of different Child-Turcotte-Pugh classes (P = .81), DOAC indications (P = .60), or DOAC dosages (P = .10). Higher proportions of patients with hepatocellular carcinoma (P = .01) had major bleeding while receiving. Patients with decompensated cirrhosis have significant bleeding and rates of discontinuation of DOACs when they take them long term. Pretreatment laboratory parameters, DOAC dose, and Child-Turcotte-Pugh class were not associated with bleeding; hepatocellular carcinoma was associated with major bleeding.

A randomized, double-blind study to evaluate the safety and tolerability of KB174, a novel synthetic glycan, in patients with well-compensated cirrhosis

A randomized, double-blind study to evaluate the safety and tolerability of KB174, a novel synthetic glycan, in patients with well-compensated cirrhosis

Exercise and physical activity in cirrhosis: opportunities or perils.

Reduced exercise capacity and impaired physical performance are observed in nearly all patients with liver cirrhosis. Physical activity and exercise are physiological anabolic stimuli that can reverse dysregulated protein homeostasis or proteostasis and potentially increase muscle mass and contractile function in healthy subjects. Cirrhosis is a state of anabolic resistance, and unlike the beneficial responses to exercise reported in physiological states, there are few systematic studies evaluating the response to exercise in cirrhosis. Hyperammonemia is a mediator of the liver-muscle axis with net skeletal muscle ammonia uptake in cirrhosis causing signaling perturbations, mitochondrial dysfunction with decreased ATP content, modifications of contractile proteins, and impaired ribosomal function, all of which contribute to anabolic resistance in cirrhosis and have the potential to impair the beneficial responses to exercise. English language-publications in peer-reviewed journals that specifically evaluated the impact of exercise in cirrhosis were reviewed. Most studies evaluated responses to endurance exercise, and readouts included peak or maximum oxygen utilization, grip strength, and functional capacity. Endurance exercise for up to 12 wk is clinically tolerated in well-compensated cirrhosis. Data on the safety of resistance exercise are conflicting. Nutritional supplements enhance the benefits of exercise in healthy subjects but have not been evaluated in cirrhosis. Whether the beneficial physiological responses with endurance exercise and increase in muscle mass with resistance exercise that occur in healthy subjects also occur in cirrhotics is not known. Specific organ-system responses, changes in body composition, or improved long-term clinical outcomes with exercise in cirrhosis need evaluation.

Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis.

Opioids are often prescribed for pain in cirrhosis and may increase the risk of hepatic encephalopathy (HE). To assess the association between opioids and HE in patients with well-compensated cirrhosis. We used the IQVIA PharMetrics (Durham, NC) database to identify patients aged 18-64years with cirrhosis. We excluded patients with any decompensation event from 1year before cirrhosis diagnosis to 6months after cirrhosis diagnosis. Over the 6months after cirrhosis diagnosis, we determined the duration of continuous opioid use and classified use into short term (1-89days) and chronic (90-180days). We assessed whether patients developed HE over the subsequent year (ie 6-18months after cirrhosis diagnosis). We used a landmark analysis and performed multivariable Cox proportional hazards regression to assess associations between opioid use and HE, adjusting for relevant confounders. The cohort included 6451 patients with compensated cirrhosis, of whom 23.3% and 4.7% had short-term and chronic opioid prescriptions respectively. Over the subsequent year, HE occurred in 6.3% patients with chronic opioid prescriptions, 5.0% with short-term opioid prescriptions and 3.3% with no opioid prescriptions. In the multivariable model, an increased risk of HE was observed with short-term (adjusted hazard ratio, HR 1.44, 95% CI 1.07-1.94) and chronic opioid prescriptions (adjusted HR 1.83, 95% CI 1.07-3.12) compared to no opioid prescriptions. In this national cohort of privately insured patients with cirrhosis, opioid prescriptions were associated with the risk of incident HE. Opioid use should be minimised in those with cirrhosis and, when required, limited to short duration.

Effective Detection of Compensated Cirrhosis Using Machine Learning

Background: Cirrhosis is often diagnosed once complications such as ascites, encephalopathy and variceal bleeding have occurred. Current non-invasive tests to detect cirrhosis have limited performance, with many patients falling into the indeterminate category. Objectives: To identify patients with well-compensated liver cirrhosis of all-causes using machine learning algorithms (MLAs) trained on routinely measured clinical and laboratory parameters. Design, Setting, and Participants: Retrospective, cross-sectional study on patients with F0, F1, and F4 fibrosis staged via biopsy at the Toronto Liver Clinic, validated on 508 patients with F0 to F4 fibrosis staged via biopsy locally as well as at the McGill University Health Centre. Patients with decompensated cirrhosis were excluded. We trained 7 MLAs to identify patients with compensated cirrhosis. Performance was benchmarked against the Aspartate aminotransferase (AST)-to-Platelet Ratio Index (APRI), Fibrosis-4 index (FIB-4), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), Transient Elastography (TE), and an independent panel of 5 experts. Results: The best MLA achieved a cross-validation area under the receiver operating characteristic curve (AUROC) of 0.88 for identifying patients with well-compensated cirrhosis, with less than 8% indeterminate classifications. The MLA achieved higher or comparable AUROC to FIB-4 on both validation sets with 20% fewer indeterminate classifications. Additionally, we show that by altering cutoffs, the MLA outperformed expert hepatologists and the NFS score and achieved superior specificity to transient elastography. Conclusion: In this study, we have demonstrated that an MLA outperforms non-imaging based methods in detecting well-compensated cirrhosis across multiple etiologies of liver disease. Our MLA was superior to APRI, FIB-4, and NFS with significantly fewer indeterminate classifications, while achieving performance comparable to an independent panel of experts. MLAs using routinely collected data could flag patients with well-compensated liver cirrhosis among patients with chronic liver disease, allowing intervention prior to onset of decompensation and associated complications. Funding Statement: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Declaration of Interests: We have no competing interests to declare. Ethics Approval Statement: Ethics approval was obtained from the Research Ethics Boards at the University Health Network, SickKids Research Institute, and MUHC.

2462 Rapid Development of Bleeding Esophageal Varices After Placement of Continuous Flow Left Ventricular Assist Device

INTRODUCTION: Upper gastrointestinal bleeding – typically due to arterio-venous malformations - is common in patients with continuous-flow LVAD, and is due to acquired von Willebrand disease and systemic anticoagulation. We present a patient with compensated cirrhosis in whom large esophageal varices developed within a few weeks of LVAD placement, resulting in hemorrhage and eventual fatal outcome. CASE DESCRIPTION/METHODS: A 62-year old male with a history of non-ischemic cardiomyopathy presented with recurrent pulmonary edema requiring intra-aortic balloon pump (IABP) to maintain stability. Workup for placement of a LVAD was initiated. An abdominal CT scan unexpectedly revealed cirrhotic liver changes. The patient had no physical exam stigmata of advanced liver disease. The INR was 1.1, platelets 170,000, albumin 3.7, transaminases and bilirubins were normal. EGD revealed no varices. A liver biopsy revealed a portal-systemic gradient of 20 mmHg and histology confirmed cirrhosis but revealed no specific etiology. The patient's MELD score of 11 and Child-Pugh class A were consistent with well-compensated cirrhosis, and the patient underwent uneventful placement of a LVAD. Seventeen days after placement, the patient sustained an acute upper GI bleeding episode. Emergent EGD revealed large, actively bleeding esophageal varices, which were successfully ligated. Over the following days, the patient developed ascites, hepatic encephalopathy and renal failure. Twelve days later, the patient developed recurrent bleeding. EGD revealed active bleeding in the esophagus and a large clot. No specific bleeding source could be identified and endoscopic attempts at hemostasis were unsuccessful. Placement of a transjugular intrahepatic portosystemic shunt was considered, but the patient's MELD score of 40 was prohibitively high. The patient continued to bleed and expired on the following morning. DISCUSSION: We hypothesize that the fluid shifts and increased hepatic arterial inflow following LVAD placement caused rapid increases in esophageal variceal pressures and bleeding. The patient's low cardiac output prior to LVAD placement likely masked the extent of his portal hypertension. In hindsight, the markedly elevated pre-LVAD portal-systemic gradient was the clearest predictor of post-LVAD variceal complications in our patient. Our experience suggests that even well-compensated cirrhotic patients with significant portal hypertension are at risk for variceal bleeding after LVAD placement.

The prognostic factors between different viral etiologies among advanced hepatocellular carcinoma patients receiving sorafenib treatment.

Sorafenib is currently the first-line therapy for advanced hepatocellular carcinoma (aHCC) patients. However, the outcomes and prognostic factors of sorafenib therapy have not been well investigated. We aimed to investigate the pretreatment factors and outcomes among Taiwanese aHCC patients receiving sorafenib treatment. A total of 347 patients with aHCC and well-compensated liver cirrhosis (Child-Pugh A) status receiving sorafenib were consecutively enrolled from March 2013 through December 2016. Pre-treatment clinical data and viral hepatitis markers were collected and analyzed with their outcomes. The primary endpoint of the study was overall survival. The factors associated with overall survival were also investigated. The median overall survival of all the patients was 238 days (range, 9-1504 days) with a 1-year overall survival of 43.2%. Positive hepatitis B surface antigen and absence of portal vein thrombosis (PVT) were independent factors associated with better overall survival. The median duration of sorafenib therapy was 93.0 days (range, 4-1504 days). After stopping sorafenib, the median survival was 93.0 days (range, 1-1254 days). The 1-year survival after stopping sorafenib was 21.2%. In chronic hepatitis B patients, total bilirubin level was the only factor associated with overall survival. Hepatitis C antibody RNA negativity, tumor size, PVT, and white blood cell count were the independent factors associated with survival among those chronic hepatitis C patients. There were different prognostic factors stratified by viral etiologies in aHCC patients receiving sorafenib. Viral eradication increased survival in chronic hepatitis C patients.

Liver Transplantation or Resection for Treatment of Hepatocellular Carcinoma in Patients with Well-Compensated Cirrhosis: A Decision Analysis Model

Hepatocellular carcinoma (HCC) is a lethal tumor, for which liver resection and transplantation are the only potentially curative treatments. No prospective, randomized study has compared survival in patients with compensated cirrhosis after the two operations. Decision analysis modeling is an objective method to quantify risks and benefits. This study aimed to use decision analysis with a Markov model to estimate the impact of liver transplant and surgical resection on survival for patients with early stage (i.e., within Milan criteria) HCC and compensated cirrhosis. The model considered waitlist drop off due to tumor progression, the probability of tumor recurrence, and the impact of hepatitis C on post-transplant survival. Peri-operative mortality was estimated as 4% after resection and 7% after transplantation. The resection group had a 67% probability of tumor recurrence at 5 years and a median survival time after recurrence of 24 months. The transplant group had a 36% probability of tumor recurrence at 5 years, and a median survival time after recurrence of 8 months. The baseline analysis of this model revealed an overall survival benefit of 2.4 years for the transplant group over the resection group. Sensitivity analyses suggest that this survival benefit remains unless the probability of recurrence in the surgical resection group decreases to less than 50% at 5 years or the transplant waitlist time is longer than 27 months. In conclusion, considering the advantages and disadvantages of each surgical therapy, liver transplantation for HCC in patients with well compensated cirrhosis due to hepatitis C is associated with better overall survival than resection over a wide range of likely scenarios.

Clinical Food Study to Evaluate the Effect of KB174 on the Gut Microbiome in Subjects With Well-compensated Cirrhosis

Clinical Food Study to Evaluate the Effect of KB174 on the Gut Microbiome in Subjects With Well-compensated Cirrhosis

Cystic fibrosis and portal hypertension: Distal splenorenal shunt can prevent the need for future liver transplant

BackgroundThe management of portal hypertension (PHT) in children with well compensated cirrhosis and cystic fibrosis (CF) is controversial. We present our experience with distal splenorenal shunting (DSRS) for the treatment of PHT as an alternative to liver transplantation (LT). MethodsBetween 2008 and 2017, 5 CF children underwent a DSRS at a pediatric hepatobiliary and transplantation referral center. LT (n = 9) was reserved for patients with decompensated cirrhosis. Statistical analysis was done using the paired t-test (p < 0.05 considered significant). ResultsMean PELD/MELD score was significantly lower for DSRS patients than LT (3 ± 6 vs 28 ± 4, p < 0.001). All 5 DSRS patients had grade III–IV varices. One bled prior to surgery. After DSRS, spleen size decreased significantly from 8.4 ± 1.5 cm to 4.4 ± 1.8 cm (p = 0.019). Mean platelet count remained stable (87.8 ± 48 to 91.8 ± 35, p = 0.9). There were no postoperative complications. No DSRS patient experienced variceal bleeding following shunt creation. Liver function tests remained stable in the DSRS group, and no patient required a liver transplant (median follow up 4.65 years, range 1.24–7.79). ConclusionsPatients with cystic fibrosis who have well-compensated cirrhosis and symptomatic portal hypertension can be palliated with distal splenorenal shunting and do not need liver transplants. These patients can undergo shunting with minimal morbidity. Type of studyCase series with no comparison group. Level of evidenceIV.

Hepatocellular Carcinoma in Transplantable Child-Pugh A Cirrhotics: Should Cost Affect Resection vs Transplantation?

BackgroundThere is no consensus regarding the optimal surgical treatment for transplantable hepatocellular carcinoma (HCC) patients with well-compensated cirrhosis. Our aim was to compare outcomes between Child-Pugh A (CPA) cirrhotics who underwent liver resection or transplantation for HCC. MethodsClinicopathologic data were retrospectively collected for all surgically treated HCC patients between 7/1992 and 12/2015. Disease-free survival (DFS) and overall survival (OS) were calculated from the time of operation or diagnosis (intention-to-treat analysis including patients removed from the transplant list). The average overall cost including pre-operative and post-operative procedures was calculated for each group. ResultsOf the 513 surgically treated HCC patients, 184 had CPA cirrhosis and fulfilled the Milan criteria (MC). Of those, 95 (52%) were resected and 89 (48%) were transplanted. Twenty-two patients were removed from the transplant list. Transplanted patients were younger (p < 0.001), had a higher MELD score (p < 0.001) and a higher frequency of hepatitis C (p < 0.001). Length of stay and postoperative complication rates were similar between groups. DFS was longer for transplanted patients (3-, 5-, and 10-year DFS rates 48, 44, 31% vs 96, 94, 94%, respectively, p < 0.001). OS was similar between groups (3-, 5-, and 10-year OS rates 76, 62, 41% vs 82, 77, 53%, respectively, p = 0.07). Only size of greatest lesion and T stage were independent predictors of OS. The cost was much higher for the transplant group, even when accounting for the treatment of recurrences ($37,391 vs $137,996). ConclusionsSince OS is similar between CPA cirrhotics within the MC undergoing resection or transplantation for HCC, but cost is significantly higher for transplantation. Resection should be considered for first-line treatment.

Cirrhosis is not a contraindication to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in highly selected patients

BackgroundPatient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is critically important to optimizing outcomes. There is currently no literature regarding the safety of CRS/HIPEC in patients with cirrhosis. The aim of this case series is to report the outcomes of three patients with well-compensated cirrhosis who underwent CRS/HIPEC.MethodsPatients were identified from a prospectively maintained peritoneal surface malignancy database. Patient, tumor, and operative-related details were recorded as short-term postoperative outcomes. Results were analyzed using descriptive statistics.ResultsAll patients had well-compensated (Child-Pugh Class A) cirrhosis and Eastern Cooperative Oncology Group (ECOG) performance status of 0. One patient had preoperative evidence of portal hypertension. All safely underwent CRS/HIPEC with completeness of cytoreduction (CC) scores of 0. The postoperative morbidity profile was unique, but all complications were manageable and resulted in full recovery to preoperative baseline status.ConclusionsPatient selection for CRS/HIPEC is critical for optimization of short- and long-term outcomes. This small series suggests that well-compensated cirrhosis should not be an absolute contraindication to CRS/HIPEC.