Clinical, Gender, Socioeconomic Characteristics and Outcomes of Individuals Receiving Hepatitis B Treatment in Ethiopia: 18-Month Follow-Up.

There is a lack of real-world data on hepatitis B (HBV) treatment in Africa. We conducted a single-center 18-month prospective cohort study in Ethiopia to understand clinical, laboratory, and demographic variables associated with HBV treatment. One hundred fifty HBV-positive patients were included: 51 on treatment, 99 with no treatment. Median age was similar between groups. Those on treatment were more likely to be male (86%), report higher coffee intake (90% versus 70%, P < 0.05), lower khat intake (0% versus 9%, P = 0.08), lower alcohol consumption (0% versus 5%, P = 0.1), and had attained higher levels of education (56% versus 42%, P = 0.19). Individuals on treatment had higher median aspartate aminotransferase (AST), alanine aminotransferase (ALT), HBV DNA, and median Aminotransferase-to-Platelet Ratio Index and Fibrosis-4 scores. At 6 and 12 months, those on treatment showed a decrease in median AST, ALT, and fibrosis scores and had less hepatocellular carcinoma development at 6 months (2% versus 4%). Our study highlights potential demographic disparities in HBV treatment as well as benefits in a real-life setting in Africa.

Assessment of STAT4 Variants and Risk of Hepatocellular Carcinoma in Latin Americans and Europeans.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The STAT4 rs7574865 genetic variant has been associated with an increased risk of developing HCC in Asian populations. However, this association has not been studied in Latin America and is poorly assessed in European populations. This case-control study investigated the association between STAT4 rs7574865 and HCC risk in these populations. We evaluated DNA samples from seven medical institutions across six Latin American countries and one Dutch institution in 1060 individuals (344 HCC and 716 controls). STAT4 rs7574865 SNP was genotyped using TaqMan-genotyping assay and analyzed using logistic regression. We found no significant association between the homozygous risk allele (G) of STAT4 and HCC development in either population, with odds ratios (OR) for GG versus TT of 0.85 (CI: 0.48-1.52, p = 0.58) and 0.81 (CI: 0.34-1.93, p = 0.67) for Latin Americans and Europeans respectively. No correlation was found between the risk allele and HCC based on underlying liver disease. However, we found that Latin Americans of European ancestry were more likely to carry the risk allele. Our results suggest that the STAT4 SNP rs7574865 does not influence the risk of developing HCC in Latin American or European populations, highlighting the importance of evaluating genetic risk factors in various ethnic groups and understanding the possible influence of ancestry on the genetic basis of disease.

Epidemiology and genetics of early onset colorectal cancer-African overview with a focus on Ethiopia.

Colorectal cancer (CRC) is a common cause of cancer-related death worldwide, with high rates of late diagnosis and increased mortality in sub-Saharan Africa. Furthermore, there is an alarming uptrend in the incidence of early onset colorectal cancer (EOCRC) across the globe, thus necessitating the need for early screening in general and special populations. There is, however, limited data available on the incidence and genetic characteristics of EOCRC from resource-poor countries, particularly Africa. Moreover, there is lack of clarity if recommendations and mechanisms proposed based on data from resource-rich countries applies to other regions of the world. In this review, we appraise the literature on EOCRC, its overall incidence, and genetic components as it pertains to sub-Saharan Africa. In addition, we highlight epidemiologic and epigenetic findings of our EOCRC cohort in Ethiopia.

Late-Onset Rejection in Liver Allograft Biopsies: An Analysis of Process, Pattern, and Clinical Implications.

OBJECTIVES: Both alloimmune and nonalloimmune factors affect the long-term survival of liver allograft recipients. Various patterns of late-onset rejection are recognized, including typical acute cellular rejection (tACR), ductopenic rejection (DuR), nonspecific hepatitis (NSH), isolated central perivenulitis (ICP), and plasma cell-rich rejection (PCRR). This study compares the clinicopathologic features of late-onset rejection (LOR) in a large-cohort context. METHODS: For-cause liver biopsies more than 6 months after transplant were included from the University of Minnesota between 2014 and 2019. Histopathologic, clinical, laboratory, treatment, and other data were analyzed in nonalloimmune and LOR cases. RESULTS: The study consisted of 160 patients (122 adults, 38 pediatric patients), with 233 (53%) biopsies showing LOR: 51 (22%) tACR; 24 (10%) DuR; 23 (10%) NSH; 19 (8%) PCRR; and 3 (1%) ICP. Mean onset of 80 vs 61 months was longer for nonalloimmune injury (P = .04), a difference lost without tACR (mean, 26 months). Graft failure was highest with DuR. Response to treatment, as measured by changes in liver function tests, was similar between tACR and other LORs, and NSH occurred more often in pediatric patients (P = .001); tACR and other LOR incidence was similar. CONCLUSIONS: LORs occur in pediatric and adult patients. Except for tACR, patterns overlap in many ways, with DuR having the greatest risk of graft loss, but other LORs respond well to antirejection treatments.

Lower survival and higher rates of cirrhosis in patients with ROUX-EN-Y gastric bypass hospitalised with alcohol-associated hepatitis.

OBJECTIVE: The incidence of alcohol-associated liver disease (ALD) is increasing, and weight loss surgery is more common due to the obesity epidemic. Roux-en-Y gastric bypass (RYGB) is associated with alcohol use disorder and ALD; however, its impact on outcomes in patients hospitalised for alcohol-associated hepatitis (AH) is unclear. DESIGN: We performed a single-centre, retrospective study of patients with AH from June 2011 to December 2019. Primary exposure was the presence of RYGB. The primary outcome was inpatient mortality. Secondary outcomes included overall mortality, readmissions and cirrhosis progression. RESULTS: 2634 patients with AH met the inclusion criteria; 153 patients had RYGB. Median age of the entire cohort was 47.3 years; median Model for End Stage Liver Disease - Sodium (MELD-Na) was 15.1 in the study group versus 10.9 in the control group. There was no difference in inpatient mortality between the two groups. On logistic regression, increased age, elevated body mass index, MELD-Na >20 and haemodialysis were all associated with higher inpatient mortality. RYGB status was associated with increased 30-day readmission (20.3% vs 11.7%, p<0.01), development of cirrhosis (37.5% vs 20.9%, p<0.01) and overall mortality (31.4% vs 24%, p=0.03). CONCLUSIONS: Patients with RYGB have higher rates of readmissions, cirrhosis and overall mortality after discharge from hospital for AH. Allocation of additional resources on discharge may improve clinical outcomes and reduce healthcare expenditure in this unique patient population.

Changing epidemiology of hepatocellular carcinoma in South America: A report from the South American liver research network.

INTRODUCTION AND OBJECTIVES: Most epidemiological data on hepatocellular carcinoma (HCC) originate from resource-rich countries. We have previously described the epidemiology of HCC in South America through the South American Liver Research Network. Here, we provide an update on the changing epidemiology of HCC in the continent seven years since that report. MATERIALS AND METHODS: We evaluated all cases of HCC diagnosed between 2019 to 2021 in centers from six countries in South America. A templated, retrospective chart review of patient characteristics at the time of HCC diagnosis, including basic demographic, clinical and laboratory data, was completed. Diagnosis of HCC was made radiologically or histologically for all cases via institutional standards. RESULTS: Centers contributed to a total of 339 HCC cases. Peru accounted for 37% (n=125) of patients; Brazil 16% (n=57); Chile 15% (n=51); Colombia 14% (n=48); Argentina 9% (n=29); and Ecuador 9% (n=29). The median age at HCC diagnosis was 67 years (IQR 59-73) and 61% were male. The most common risk factor was nonalcoholic fatty liver disease (NAFLD, 37%), followed by hepatitis C (17%), alcohol use disorder (11%) and hepatitis B (12%). The majority of HCCs occurred in the setting of cirrhosis (80%). HBV-related HCC occurred at a younger age compared to other causes, with a median age of 46 years (IQR 36-64). CONCLUSIONS: We report dramatic changes in the epidemiology of HCC in South America over the last decade, with a substantial increase in NAFLD-related HCC. HBV-related HCC still occurs at a much younger age when compared to other causes.

Viral Hepatitis Among African Immigrants with Hepatocellular Carcinoma in Minnesota: High Prevalence Yet Low Awareness.

We aimed to study the virologic profile of immigrants from Africa with viral hepatitis-related hepatocellular carcinoma (HCC) who received care at our institution. We conducted a descriptive study among African-born patients with HCC who received care at University of Minnesota Medical Center from 2011 to 2018. We analyzed the prevalence, virologic profiles and treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections prior to HCC diagnosis. 74 African-born patients with HCC were eligible for analysis. 54 had HCV and 20 had HBV infection. 80% of HBV patients were treated but remained with inadequate viral suppression at the time of HCC diagnosis while only 39% of HCV patients were treated prior to HCC diagnosis. Lost to follow up was common in both groups. Our findings suggest that there is a significant gap in appropriate viral hepatitis care in an African immigrant population in Minnesota. Culturally-appropriate strategies are needed to bridge this gap.

Hepatocellular carcinoma in Hepatitis B and Human Immunodeficiency Virus coinfection in Africa: a focus on surveillance.

Human immunodeficiency virus (HIV) and hepatitis-B virus (HBV) infections are weighty public health challenges, especially in the African continent. The direct carcinogenic effect of HBV means that it remains a potent cause of early-onset hepatocellular carcinoma (HCC) in Sub-Saharan Africa (SSA), where it causes significant morbidity and mortality. The presence of HIV infection in HBV-infected patients poses a complicating factor, as coinfection has been shown to hasten the progression of liver disease to cirrhosis and HCC, and often resulting in early-age hepatocarcinogenesis with consequent late diagnosis and lower survival. In this review, we discuss this unique conundrum, the epidemiology of HIV-HBV coinfection in SSA, its effect on liver disease and development of HCC, as well as practices and barriers to HCC surveillance in this distinct population. We propose a way forward to curb this considerable health burden focusing on reduction of disease stigma, the need for easy-to-measure biomarkers, and implementation of large prospective studies in this population.

Hepatitis E virus infection in the United States: Seroprevalence, risk factors and the influence of immunological assays.

In the United States (U.S.), a hepatitis E virus (HEV) seroprevalence between 6 and 21% has been described, with a decreasing trend. We aimed to investigate HEV infection in the U.S. population from 2009 to 2016, and examine the differences in seroprevalence using different assays. We used data from the National Health and Nutrition Examination Survey (NHANES-CDC) to estimate HEV seroprevalence and analyze demographic variables related to the infection. Additionally, we compared 4 serological tests used. The estimated HEV seroprevalence between 2009-2016 was 6.1% (95% CI: 5.6%-7.0%) for IgG and 1.02% (0.8%-1.2%) for IgM. Higher HEV IgG prevalences were found in older people, females, non-Hispanic Asians and those born outside of the U.S. The in-house immunoassay and the Wantai HEV-IgG ELISA presented the highest sensitivity values in the tested population. The highest specificity values corresponded to the DSI-EIA-ANTI-HEV-IgG assay. The kappa statistical values showed concordances no greater than 0.64 between the assays. HEV prevalence in our study was similar to previously reported, and a decline in the prevalence was observed through the NHANES assessments (from 1988 to 2016). The sensitivity and specificity of the assays varied widely, making comparisons difficult and highlighting the need to develop a gold standard assay.

Case of Primary Hepatic Angiosarcoma Presenting With Jaundice and Infiltrative Liver Masses.

Primary hepatic angiosarcoma (PHA) is a rare and aggressive mesenchymal liver tumor with a poor prognosis and high mortality. Treatment options are limited to palliative chemotherapy with surgical resection reserved for the few cases that present early. We present a case of a patient who presented with jaundice and elevated liver enzymes. Imaging identified a diffusely heterogeneous liver consistent with cirrhosis, findings of portal hypertension, and 2 ill-defined liver lesions. Biopsy results confirmed PHA. Primary hepatic angiosarcoma does not have a typical presentation but should be considered for any patient presenting with an infiltrative liver mass.

Understanding immune perspectives and options for the use of checkpoint immunotherapy in HCC post liver transplant.

Treatment modalities for hepatocellular carcinoma (HCC) vary from surgical techniques and interventional radiologic strategies to systemic therapy. For the latter, the use of immune checkpoint inhibitors (ICIs) has gained popularity due to successful trials showing increased survival. In patients who have undergone liver transplantation, recurrence of HCC poses a significant challenge. There is indeed considerable debate on the efficacy and safety of ICI use in liver transplant recipients due to competing immune interests in maintaining a healthy graft and combating the tumor. Recent reports and case series have highlighted a role for the type of immune therapy, timing of therapy, tissue expression of PD-1 and modulation of immunosuppression, in the understanding of the efficacy and risks of ICIs for HCC in liver transplant. In this article, we appraise the available literature on the usage of ICIs for HCC in liver transplant recipients and provide perspectives on immune concerns as well as potential recommendations to consider during the management of such complex cases.

The Role of Cytokines in the Different Stages of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the primary form of liver cancer and a leading cause of cancer-related death worldwide. Early detection remains the most effective strategy in HCC management. However, the spectrum of underlying liver diseases preceding HCC, its genetic complexity, and the lack of symptomatology in early stages challenge early detection. Regardless of underlying etiology, unresolved chronic inflammation is a common denominator in HCC. Hence, many inflammatory molecules, including cytokines, have been investigated as potential biomarkers to predict different stages of HCC. Soluble cytokines carry cell-signaling functions and are easy to detect in the bloodstream. However, its biomarkers' role remains limited due to the dysregulation of immune parameters related to the primary liver process and their ability to differentiate carcinogenesis from the underlying disease. In this review, we discuss and provide insight on cytokines with clinical relevance for HCC differentiating those implicated in tumor formation, early detection, advanced disease, and response to therapy.

A Case of Infiltrative Hepatocellular Carcinoma With Vascular Invasion Into the Heart.

Hepatocellular carcinoma (HCC) represents a major cause of morbidity and mortality in the world, but this problem is especially significant in low-resource countries where HCC screening recommendations and strategies are limited. We describe a rare complication of newly diagnosed HCC in a patient with untreated hepatitis B virus (HBV) infection, underscoring the importance of improving screening strategies and promoting early diagnosis of HCC in Sub-Saharan Africa.

L-Asparaginase-Induced Hepatotoxicity Treated Successfully With L-Carnitine and Vitamin B Infusion.

Asparaginase plays an integral role in chemotherapy for acute lymphoblastic leukemia (ALL). We present a 69-year old woman with refractory ALL, who developed asparaginase-induced hepatotoxicity and cholangiopathy after starting intravenous PEG-L-asparaginase-based chemotherapy. The patient was ultimately treated with the combination of L-carnitine and vitamin B complex, resulting in normalization of liver enzymes levels. This case highlights the consideration of PEG-L asparaginase chemotherapy-induced liver steatosis, injury, and cholangiopathy as well as the role of L-carnitine and vitamin B complex as treatment.

Thyroid Disease-Induced Hepatic Dysfunction: A Clinical Puzzle.

The diagnostic evaluation of an individual with clinical and laboratory evidence of thyroid dysfunction in the setting of acute liver injury is crucial. There is a complex relationship between the thyroid and the liver, and so, it requires a careful elucidation of the inciting disease process before instituting a treatment plan. We discuss a patient who had presented with coagulopathy, encephalopathy, and laboratory evidence of acute liver injury, hence adjudged to have developed drug-induced acute liver failure and transferred for liver transplant evaluation. She was found to have liver dysfunction from uncontrolled thyroid disease, with immediate and rapid improvement after controlling severe hyperthyroidism.

Hepatitis B-related hepatocellular carcinoma: surveillance strategy directed by immune-epidemiology.

Hepatitis B infection (HBV) is one of the most common causes of hepatocellular carcinoma (HCC) worldwide. The age of occurrence, prognosis and incidence vary dramatically depending on the region of the world. This geographic variation is largely dependent on the contrasting incidence of HBV, age of transmission of the virus, the timing of integration into the human genome, and different HBV genotypes, as well as environmental factors. It results in a wide difference in viral interaction with the immune system, genomic modulation and the consequent development of HCC in an individual. In this review, we describe many factors implicated in HCC development, provide insight regarding at-risk populations and explain societal recommendations for HCC surveillance in persons living with HBV in different continents of the world.

Assessment of subclinical effects of Hepatitis E virus infection in the United States.

Some studies have exposed an increase in liver cirrhosis in hepatitis E seropositive individuals living with human immunodeficiency virus. The interrelation between HEV seroprevalence and risk of liver disease in immune-competent individuals remains under- investigated. Using the National Health and Nutrition Examination Survey (NHANES) data containing >30,000 subjects, we addressed if HEV exposure leads to subclinical effects that can influence liver health. We determined the association between HEV IgM and ALT and that of HEV IgG and Fib-4-a composite score reflecting potential liver fibrosis. These analyses were repeated in populations at risk for liver disease as well as among different races and ethnicities. The prevalence of HEV IgG was significantly associated with age as IgG positive individuals were, on average, 20 years older than IgG negative patients. We found a statistically significant increase in the likelihood of having a Fib-4 score >1.45 (significant fibrosis) in those positive for HEV IgG (RR: 1.03; 95% CI: 1.01-1.05). However, due to the small effect, it is unlikely that this association has clinical significance. Moreover, the effect was not present in those with pre-existing liver disease. We found no association between ALT levels and the presence of HEV IgM or IgG. This is the first study examining subclinical effects of HEV infection in the United States. Our study found that in the general US population, predominantly asymptomatic HEV infections do not contribute to the overall burden of liver disease.