Single center analysis of therapy and outcomes of hepatocellular carcinoma in Sub-Saharan Africa.

PURPOSE: To evaluate the characteristics and response to therapy for HCC in sub-Saharan Africa. PATIENTS AND METHODS: We retrospectively evaluated demographic, clinical and outcome variables of HCC in a referral clinic in Ethiopia from 2016 to 2018. Survival assessment was performed using the Mann-Whitney test. Associations between categorical variables was assessed using Pearson Chi-square test. RESULTS: We report 46 HCC cases with a median age of 54 years (IQR 45-62) and 50% female. Viral hepatitis was the most common underlying etiology, with 41% of subjects infected with hepatitis B virus (HBV) and 45% with hepatitis C. The median MELD was 12 (IQR 8-17), we found no association between survival and a MELD score 15, regardless of underlying disease (pr=0.61, p>0.05). 31% of individuals underwent supportive treatment with a median survival of 27 days (IQR 19-181), 18% used Sorafenib (median survival of 94 days, IQR 24-121), and trans-arterial chemoembolization (TACE) was utilized in 16% (median survival of 352 days, IQR 30-436). HBV cases were diagnosed younger (31% before the age of 40) and those on Tenofovir had a longer median survival than those off Tenofovir (121 vs 34 days). CONCLUSION: Our study found that antiviral treatment of HBV infection was associated with longer survival in HCC. Furthermore, Sorafenib seemed beneficial in patients that used this modality and NLR was a good prognostic factor.

Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation.

BACKGROUND: Liver transplantation (LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality. Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered. AIM: To assess the impact of pre-transplant iron metabolism parameters on post-transplant survival. METHODS: From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin (SF) and transferrin saturation (TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death. RESULTS: At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS > 75% [HR: 1.73 (1.14; 2.63)], SF < 100 µg/L [HR: 1.62 (1.12; 2.35)], hepatocellular carcinoma [HR: 1.58 (1.15; 2.26)], estimated glomerular filtration rate (CKD EPI Cystatin C) [HR: 0.99 (0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05 (1.03; 1.08)]. Kaplan Meier curves show that patients with low SF (< 100 µg/L) or high SF (> 400 µg/L) have lower survival rates at 36 mo than patients with normal SF (P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo (91.4% ± 1.4% vs 84.6% ± 3.1%, P = 0.039). TS > 75% was significantly associated with infection related death [HR: 3.06 (1.13; 8.23)]. CONCLUSION: Our results show that iron metabolism imbalance (either deficiency or overload) is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.

Palliative long-term abdominal drains versus repeated drainage in individuals with untreatable ascites due to advanced cirrhosis: study protocol for a feasibility randomised controlled trial.

BACKGROUND: UK deaths due to chronic liver diseases such as cirrhosis have quadrupled over the last 40 years, making this condition now the third most common cause of premature death. Most patients with advanced cirrhosis (end-stage liver disease [ESLD]) develop ascites. This is often managed with diuretics, but if refractory, then the fluid is drained from the peritoneal cavity every 10-14 days by large volume paracentesis (LVP), a procedure requiring hospital admissions. As the life expectancy of patients with ESLD and refractory ascites (if ineligible for liver transplantation) is on average ≤ 6 months, frequent hospital visits are inappropriate from a palliative perspective. One alternative is long-term abdominal drains (LTADs), used successfully in patients whose ascites is due to malignancy. Although inserted in hospital, these drains allow ascites management outside of a hospital setting. LTADs have not been formally evaluated in patients with refractory ascites due to ESLD. METHODS/DESIGN: Due to uncertainty about appropriate outcome measures and whether patients with ESLD would wish or be able to participate in a study, a feasibility randomised controlled trial (RCT) was designed. Patients were consulted on trial design. We plan to recruit 48 patients with refractory ascites and randomise them (1:1) to either (1) LTAD or (2) current standard of care (LVP) for 12 weeks. Outcomes of interest include acceptability of the LTAD to patients, carers and healthcare professionals as well as recruitment and retention rates. The Integrated Palliative care Outcome Scale, the Short Form Liver Disease Quality of Life questionnaire, the EuroQol 5 dimensions instrument and carer-reported (Zarit Burden Interview) outcomes will also be assessed. Preliminary data on cost-effectiveness will be collected, and patients and healthcare professionals will be interviewed about their experience of the trial with a view to identifying barriers to recruitment. DISCUSSION: LTADs could potentially improve end-of-life care in patients with refractory ascites due to ESLD by improving symptom control, reducing hospital visits and enabling some self-management. Our trial is designed to see if such patients can be recruited, as well as to inform the design of a subsequent definitive trial. TRIAL REGISTRATION: ISRCTN, ISRCTN30697116 . Registered on 7 October 2015.

Coffee consumption protects against progression in liver cirrhosis and increases long-term survival after liver transplantation.

BACKGROUND: Therapeutic options to treat progression of end-stage liver disease (ESLD) or improve long-term survival after liver transplantation remain scarce. We investigated the impact of coffee consumption under these conditions. METHODS: We recorded coffee consumption habits of 379 patients with ESLD awaiting liver transplantation and 260 patients after liver transplantation. Survival was analyzed based on coffee intake. RESULTS: One hundred ninety-five patients with ESLD consumed coffee on a daily basis, while 184 patients did not. Actuarial survival was impaired (P = 0.041) in non-coffee drinkers (40.4 ± 4.3 months, 95% confidence interval [CI]: 32.0-48.9) compared with coffee drinkers (54.9 ± 5.5 months, 95% CI: 44.0-65.7). In subgroup analysis, the survival of patients with alcoholic liver disease (ALD; P = 0.020) and primary sclerosing cholangitis (PSC; P = 0.017) was increased with coffee intake while unaffected in patients with chronic viral hepatitis (P = 0.517) or other liver disease entities (P = 0.652). Multivariate analysis showed that coffee consumption of PSC and ALD patients retained as an independent risk factor (odds ratio [OR]: 1.94; 95% CI: 1.15-3.28; P = 0.013) along with MELD score (OR: 1.13; 95% CI: 1.09-1.17; P = 0.000). Following liver transplantation, long-term survival was longer in coffee drinkers (coffee: 61.8 ± 2.0 months, 95% CI: 57.9-65.8) than non-drinkers (52.3 ± 3.5 months, 95% CI: 45.4-59.3; P = 0.001). CONCLUSIONS: Coffee consumption delayed disease progression in ALD and PSC patients with ESLD and increased long-term survival after liver transplantation. We conclude that regular coffee intake might be recommended for these patients.

Lessons Learned From Review of a Single Center Experience With 500 Consecutive Liver Transplants in a Region With Insufficient Deceased-Donor Support.

OBJECTIVES: We present here the outcomes of our first 500 liver transplants and discuss the lessons learned during this time. MATERIALS AND METHODS: We retrospectively analyzed the first 500 consecutive transplants within the listing criteria of the United Network for Organ Sharing, with recipients and donors with minimum 1-year follow-up. Patient survival and donor complications were analyzed for 31 liver transplant recipients with hepatocellular carcinoma beyond the Milan criteria who had transplant performed during the same time. RESULTS: Between August 2006 and March 2013, there were 519 liver transplants performed in 500 patients (365 adult, 135 pediatric). There were 394 living-donor and 125 deceased-donor liver transplants. In addition, 31 adult liver transplants were performed in patients with hepatocellular carcinoma beyond Milan criteria (22 living-donor and 9 deceased-donor transplants). The main cause of chronic liver failure was biliary atresia in pediatric patients (30.4%) and chronic hepatitis B infection in adults (35.6%). The complication rate for primary nonfunction was 3.8%, overall biliary complications 24.0% (significantly higher after adult living-donor liver transplant, 30.3%), hepatic artery thrombosis 1.6%, portal vein thrombosis 3.0%, retransplant 3.8%, acute cellular rejection 29.6%, and bacterial infection 39.4%. Overall 1-, 3-, and 5-year patient survival rates in the first 500 consecutive transplants performed on recipients within United Network for Organ Sharing listing criteria were 87.8%, 85.0%, and 78.6%; for hepatocellular carcinoma patients beyond the Milan criteria, survival rates were 71.9%, 52.5%, and 38.2%. CONCLUSIONS: In regions without a sufficient number of deceased donors, living-donor liver transplant, with its associated problems, is the only alternative to deceased-donor liver transplant. Liver transplant requires teamwork, with all players working well together for a successful outcome. The important keys to success in liver transplant include decision-making, timing, surgical skills, experience, and close follow-up.

Model for end-stage liver disease score as a predictor of short-term outcome in patients with drug-induced liver injury.

OBJECTIVES: The purposes of this study were to investigate the clinical presentation, cause and outcome of drug-induced liver injury (DILI) and to evaluate the predictive value of the model for end-stage liver disease (MELD) score in DILI. METHODS: Patients diagnosed with DILI between January 1, 2010 and December 31, 2012 in the Emergency Department at Asan Medical Center in Seoul, Korea were analyzed retrospectively. The primary end point was poor outcome, defined as liver transplantation or death within 30 days of the initial hospital visit. RESULTS: Of 213 patients, 13.1% had a 30-day poor outcome. Folk remedies were the most common cause of DILI in 147 patients (69%). Univariate logistic regression analysis showed that multiple drugs (odds ratio [OR] 2.30, 95% confidence interval [CI]: 1.03-5.15), concurrent alcohol consumption (OR 3.69, 95% CI: 1.03-13.18), white blood cell (WBC) count (OR 1.17, 95% CI: 1.07-1.28), hemoglobin (Hb) (OR 0.60, 95% CI: 0.49-0.74), platelet count (OR 0.993, 95% CI: 0.987-0.998), total bilirubin (OR 1.09, 95% CI: 1.06-1.13) and MELD (OR 1.23, 95% CI: 1.15-1.32) were significantly associated with 30-day poor outcomes. Multivariate analysis showed that the MELD (OR 1.21, 95% CI: 1.12-1.30) and Hb (OR 0.77, 95% CI: 0.61-0.98) were independent predictors of poor outcome. For 30-day mortality, the c-statistics for MELD alone and for combination of MELD and Hb were 0.93 (95% CI: 0.89-0.97) and 0.94 (95% CI: 0.90-0.97), respectively. CONCLUSION: The outcome of patients with DILI was poor. MELD score and Hb were reliable predictors of short-term outcome in patients with DILI.

[A prospective cohort study on the influence of high doses of herbs for clearing heat and resolving stasis on survival rates in patients with hepatitis B-related acute-on-chronic liver failure].

BACKGROUND: Hepatitis B-related acute-on-chronic liver failure (ACLF) is a severe clinical syndrome characterized by jaundice, coagulopathy, ascites and hepatic encephalopathy and with a high mortality rate of 65% to 93%. It involves significant ethical issues when a randomized, double-blinded, placebo-controlled clinical study is conducted to such a serious disease. Therefore, a prospective cohort study design was utilized to explore a new treatment modality of applying integrated traditional Chinese and Western medicine. OBJECTIVE: To evaluate the efficacy, safety and recent survival rates of high-dose herbs with the function of clearing heat and resolving stasis, named Qingre Huayu, in patients with hepatitis B-related ACLF with heat toxin stagnation syndrome. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A matched, prospective cohort study was conducted. Participants who met the inclusion criteria were recruited from the Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. Patients were assigned to either an integrated medicine group or a Western medicine group according to their own preference and received either a regime of classic Western medical treatment (control group) or a regime of classic Western medical treatment plus Qingre Huayu herbs (treatment group). The regimes were conducted for 12 weeks. MAIN OUTCOME MEASURES: Survival rates of non-liver transplantation patients were evaluated after 12-week treatment. The levels of total bilirubin (TBiL), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and prothrombin activity (PTA) were detected at baseline and weeks 4, 8 and 12. Scores of traditional Chinese medicine (TCM) syndrome and complications were evaluated at baseline and study completion. Adverse events were recorded. RESULTS: All patients were followed up to the deadline for this study. There were 21 cases (31.8%) who died in the treatment group (n=66) and 19 cases (59.4%) in the control group (n=32). Significant difference (X(2)=6.775, P<0.01) was found in comparing the survival and death rates between the two groups by X(2) test. At 12 weeks, mean survival time of the two groups was 69.9 and 47.2 d respectively; cumulative survival rate of patients in the treatment group was higher than that of patients in the control group (P<0.01). Levels of TBiL, ALT, AST, ALB and PTA at weeks 4, 8 and 12 in the treatment group were superior to those in the control group with statistical significance (P<0.01 or P<0.05). In comparison of the TCM syndrome scores at week 12, the average score of the TCM syndrome of the treatment group (n=45) was 7.52±2.41, lower than 18.34±4.36 of the control group (n=13), and the difference was significant (t=8.784, P<0.01). Complication incidences after 12 weeks of treatment were statistically different between the treatment group (n=45) and the control group (n=13) by X(2) test (P<0.05 or P<0.01). Incidence rates of ascites, infection and hepatic encephalopathy accounted for 22.22%(10/45) and 69.23% (9/13), 8.89% (4/45) and 53.85% (7/13), and 11.11% (5/45) and 46.15% (6/13) in the two groups respectively. The incidence rates of adverse events in the treatment group and the control group were 0.00% and 12.50% respectively and the difference was statistically significant (X(2)=5.705, P<0.05). No drug-related adverse events were found in blood, urine and stool routine tests, renal function test and electrocardiography. CONCLUSION: High doses of Qingre Huayu herbs can significantly improve liver function and coagulation function, reduce complications, and reduce mortality in patients with hepatitis B-related ACLF.