Recurrent hepatic encephalopathy (HE) is a leading cause of readmission despite standard of care (SOC) associated with microbial dysbiosis. Fecal microbiota transplantation (FMT) may improve ...dysbiosis; however, it has not been studied in HE. We aimed to define whether FMT using a rationally derived stool donor is safe in recurrent HE compared to SOC alone. An open‐label, randomized clinical trial with a 5‐month follow‐up in outpatient men with cirrhosis with recurrent HE on SOC was conducted with 1:1 randomization. FMT‐randomized patients received 5 days of broad‐spectrum antibiotic pretreatment, then a single FMT enema from the same donor with the optimal microbiota deficient in HE. Follow‐up occurred on days 5, 6, 12, 35, and 150 postrandomization. The primary outcome was safety of FMT compared to SOC using FMT‐related serious adverse events (SAEs). Secondary outcomes were adverse events, cognition, microbiota, and metabolomic changes. Participants in both arms were similar on all baseline criteria and were followed until study end. FMT with antibiotic pretreatment was well tolerated. Eight (80%) SOC participants had a total of 11 SAEs compared to 2 (20%) FMT participants with SAEs (both FMT unrelated; P = 0.02). Five SOC and no FMT participants developed further HE (P = 0.03). Cognition improved in the FMT, but not the SOC, group. Model for End‐Stage Liver Disease (MELD) score transiently worsened postantibiotics, but reverted to baseline post‐FMT. Postantibiotics, beneficial taxa, and microbial diversity reduction occurred with Proteobacteria expansion. However, FMT increased diversity and beneficial taxa. SOC microbiota and MELD score remained similar throughout. Conclusion: FMT from a rationally selected donor reduced hospitalizations, improved cognition, and dysbiosis in cirrhosis with recurrent HE. (Hepatology 2017;66:1727–1738)
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•Choledochal cysts were found to be most strongly associated with both iCCA and eCCA.•Cirrhosis was a significant CCA risk, with a stronger association with iCCA than ...eCCA.•Choledocholithiasis had a stronger association with eCCA than iCCA.•In Eastern countries, cirrhosis and HBV conferred a greater risk of iCCA than in Western countries.•Rising global incidence of iCCA may be linked to increases in T2DM, cirrhosis, alcoholic liver disease and cholelithiasis.
Cholangiocarcinoma (CCA) carries a poor prognosis, is increasing in incidence and its causes are poorly understood. Although some risk factors are known, they vary globally and collectively account for a minority of cases. The aim of this study was to perform a comprehensive meta-analysis of risk factors for intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA), from Eastern and Western world studies.
A literature search of case-control studies was performed to identify potential risk factors for iCCA and eCCA. Pooled odds ratios (ORs) with 95% CIs and heterogeneity were calculated. Funnel plots were used to assess publication bias, and meta-regression was used to select risk factors for comparison between Eastern and Western studies.
A total of 13 risk factors were selected from 25 case-control studies in 7 geographically diverse countries. The strongest risk factors for both iCCA and eCCA were biliary cysts and stones, cirrhosis, hepatitis B and hepatitis C. Choledochal cysts conferred the greatest risk of both iCCA and eCCA with pooled ORs of 26.71 (95% CI 15.80–45.16) and 34.94 (24.36–50.12), respectively. No significant associations were found between hypertension and obesity for either iCCA or eCCA. Comparing Eastern and Western populations, there was a difference for the association of hepatitis B with iCCA (coefficient = −0.15195; 95% CI −0.278 to −0.025; p = 0.022).
This is the most comprehensive meta-analysis of CCA risk factors to date. Some risk factors, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of this cancer.
Cholangiocarcinoma (CCA) is a cancer arising in the bile ducts inside (intrahepatic CCA) and connected to the liver (extrahepatic CCA). It is a very aggressive cancer: 95% of patients die within 5 years. CCA rates are increasing globally, but the causes of CCA are poorly understood. The few risk factors that are known account for only a minority of cases. In this study, we found that the strongest risk factors for both intrahepatic and extrahepatic CCA are cysts and stones in the bile ducts, cirrhosis, and hepatitis B and C viruses. Some risk factors for CCA, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of CCA.
Healthcare systems in Africa suffer from neglect and underfunding, leading to severe challenges across the six World Health Organization (WHO) pillars of healthcare delivery. We conducted this study ...to identify the principal challenges in the health sector in Africa and their solutions for evidence-based decisions, policy development and program prioritization.
The study was conducted as part of a recent African Epidemiological Association Meeting in Maputo, Mozambique with participants drawn from 11 African countries, Cuba, Portugal and the United Kingdom. Participants were divided into 10 groups, consisting of 7 to 10 persons each. Brainstorming approaches were used in a structured, modified nominal group process exercise to identify key challenges and strategies to mitigate healthcare service challenges in Africa. Identified challenges and solutions were prioritised by ranking 1-5, with 1 most important and 5 being least important.
The first three challenges identified were inadequate human resources (34.29%), inadequate budgetary allocation to health (30%) and poor leadership and management (8.45%). The leading solutions suggested included training and capacity building for health workers (29.69%), increase budgetary allocation to health (20.31%) and advocacy for political support and commitment (12.31%).
The underdeveloped healthcare systems in Africa need radical solutions with innovative thought to break the current impasse in service delivery. For example, public-private initiatives should be sought, where multinational companies extracting resources from Africa might be encouraged to plough some of the profits back into healthcare for the communities providing the workforce for their commercial activities. Most problems and their solutions lie within human resources, budget allocation and management. These should be accorded the highest priority for better health outcomes.
Hepatocellular carcinoma （HCC） is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of ...alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.
Background
Although novel hepatitis C virus (HCV) RNA point‐of‐care technology has the potential to enhance the diagnosis in resource‐limited settings, very little real‐world validation of their ...utility exists. We evaluate the performance of HCV RNA quantification using the Xpert® HCV viral load Fingerstick assay (Xpert® HCV VL Fingerstick assay) as compared to the World Health Organisation pre‐qualified plasma Xpert® HCV VL assay among people who inject drugs (PWID) attending an opioid agonist therapy (OAT) clinic in Dar‐es‐Salaam, Tanzania.
Methods
Between December 2018 and February 2019, consecutive HCV seropositive PWID attending the OAT clinic provided paired venous and Fingerstick samples for HCV RNA quantification. These were processed onsite using the GeneXpert® platform located at the Central tuberculosis reference laboratory.
Results
A total of 208 out of 220 anti‐HCV‐positive participants recruited (94.5%) had a valid Xpert® HCV VL result available; 126 (61%; 95% CI 53.8‐67.0) had detectable and quantifiable HCV RNA. About 188 (85%) participants had paired plasma and Fingerstick whole blood samples; the sensitivity and specificity for the quantification of HCV RNA levels were 99.1% and 98.7% respectively. There was an excellent correlation (R2 = .95) and concordance (mean difference 0.13 IU/mL, (95% CI −0.9 to 0.16 IU/mL) in HCV RNA levels between plasma samples and Fingerstick samples.
Conclusion
This study found excellent performance of the Xpert® HCV VL Fingerstick assay for HCV RNA detection and quantification in an African‐field setting. Its clinical utility represents an important watershed in overcoming existing challenges to HCV diagnosis, which should play a crucial role in HCV elimination in Africa.
Liver transplantation (LT) improves daily function and ameliorates gut microbial composition. However, the effect of LT on microbial functionality, which can be related to overall patient benefit, is ...unclear and could affect the post‐LT course. The aims were to determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism, and lipidomics. We enrolled outpatient patients with cirrhosis on the LT list and followed them until 6 months after LT. Microbiota composition (Shannon diversity and individual taxa) and function analysis (serum endotoxin, urinary metabolomics and serum lipidomics, and stool BA profile) and cognitive tests were performed at both visits. We enrolled 40 patients (age, 56 ± 7 years; mean Model for End‐Stage Liver Disease score, 22.6). They received LT 6 ± 3 months after enrollment and were re‐evaluated 7 ± 3 months after LT with a stable course. A significant improvement in cognition with increase in microbial diversity, increase in autochthonous and decrease in potentially pathogenic taxa, and reduced endotoxemia were seen after LT compared with baseline. Stool BAs increased significantly after LT, and there was evidence of greater bacterial action (higher secondary, oxo and iso‐BAs) after LT although the levels of conjugated BAs remained similar. There was a reduced serum ammonia and corresponding rise in urinary phenylacetylglutamine after LT. There was an increase in urinary trimethylamine‐N‐oxide, which was correlated with specific changes in serum lipids related to cell membrane products. The ultimate post‐LT lipidomic profile appeared beneficial compared with the profile before LT. In conclusion, LT improves gut microbiota diversity and dysbiosis, which is accompanied by favorable changes in gut microbial functionality corresponding to BAs, ammonia, endotoxemia, lipidomic, and metabolomic profiles. Liver Transplantation 24 752–761 2018 AASLD.
Non-communicable diseases (NCDs) are the leading cause of death globally, the majority of these being due to cardiovascular disease, cancer, chronic respiratory diseases, or diabetes. Mortality from ...many NCDs continues to increase worldwide, with a disproportionately larger impact in low-middle income countries (LMIs), where almost 75% of global deaths occur from these causes. As a low-income African country that consistently ranks amongst the world's poorest nations, Malawi as a case study demonstrates how transition due to societal change and increasing urbanization is often accompanied by a rise in the rate of NCDs. Other factors apart from changing lifestyle factors can explain at least some of this increase, such as the complex relationship between communicable and NCD and growing environmental, occupational, and cultural pressures. Malawi and other LMIs are struggling to manage the increasing challenge of NCDs, in addition to an already high communicable disease burden. However, health care policy implementation, specific health promotion campaigns, and further epidemiological research may be key to attenuating this impending health crisis, both in Malawi and elsewhere. This review aims to examine the effects of the major NCDs in Malawi to help inform future public health care policy in the region.
Summary
The World Health Organisation has recently called for hepatitis C virus (HCV) elimination and has identified people who inject drugs (PWID) as a key population to scale‐up screening and ...linkage to care. This study reports the cascade of care for HCV in PWID attending the largest opioid substitution treatment (OST) clinic in Dar‐es‐Salaam, Tanzania. Between February 2011 and March 2016, HCV serology for all PWID registered at the Muhimbili National Hospital OST clinic, Dar‐es‐Salaam were obtained from records. In 2015, consecutive HCV‐seropositive PWID were invited to undergo a clinical evaluation including epidemiological questionnaire, liver stiffness measurement (Fibroscan) and virological analysis (HCV RNA viral load and genotyping). During the study period, 1350 persons registered at the OST clinic: all had a HCV serology including 409 (30%) positive results. Among the HCV‐seropositive individuals, 207 (51%) were active attenders and 153 (37%) were enrolled for clinical assessment: 141 (92%) were male, median age: 38 years (IQR 34‐41), and 65 (44%) were co‐infected with HIV; 116 patients (76%) had detectable HCV RNA, with genotypes 1a (68%) and 4a (32%); 21 (17%) had clinically significant fibrosis (≥F2) and 6 (5%) had cirrhosis (F4). None were offered HCV treatment. Chronic hepatitis C among PWID enrolled in the OST centre in Dar‐es‐Salaam is frequent, but its continuum of care is insufficient; integration of HCV diagnosis and treatment should form a part of OST intervention in PWID in Tanzania.
Summary
Blood transfusion is one of the most commonly relied upon therapies in sub‐Saharan Africa. Existing safeguards recommended include systematic screening for transfusion‐transmitted infections ...and restricted voluntary nonremunerated blood donor selection. We report the transfusion‐transmitted infection screening and notification practice at a large urban blood transfusion centre in Dar‐es‐Salaam, Tanzania. Between October 2016 and March 2017 anonymized records of all donors registered at the blood transfusion unit were accessed to retrospectively note demographic information, donor status, first‐time status, transfusion‐transmitted infection result and notification. 6402 consecutive donors were screened for transfusion‐transmitted infections; the majority were family/replacement blood donors (88.0%) and male (83.8%). Overall transfusion‐transmitted infections prevalence was 8.4% (95% CI 7.8‐9.1), with hepatitis B being the most prevalent infection (4.1% (95% CI 3.6‐4.6)). Transfusion‐transmitted infections were more common in family/replacement blood donors (9.0% (95% CI 8.3‐9.8)) as compared to voluntary nonremunerated blood donor (4.1% (95% CI 2.8‐5.7)). A minority of infected‐donors were notified of a positive result (8.5% (95% CI 6.3‐11.2)). Although transfusion‐transmitted infections are more prevalent among family/replacement blood donors, overall risk of transfusion‐transmitted infections across all groups is considerable. In addition, existing efforts to notify donors of a positive transfusion‐transmitted infection are poor. Future policies must focus on improving linkage to care for newly diagnosed patients with transfusion‐transmitted infections.
Background & Aims
Dietary changes can modulate gut microbiota and interact with cirrhosis. Our prior study demonstrated that microbial diversity was higher in cirrhotics from Turkish vs the USA, ...which was associated with lower risk of 90‐day hospitalizations. We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets.
Methods
In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied. Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet. Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries. Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated.
Results
Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA. Plasma metabolomics demonstrated higher relative lactate levels in Turkey vs the USA. The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and the USA, with reduced lipids and phosphocholines. Phosphocholines were significantly lower in patients hospitalized in 90 days (P = .03). Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients.
Conclusions
A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis. These altered diet‐microbial interactions could potentially affect the 90‐day hospitalization risk.
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