The gut-immune-liver axis in patients with alcohol use disorder and clinically low serum zinc levels.

BACKGROUND: Alcohol use disorder (AUD) with chronic and heavy alcohol consumption causes alcohol-associated liver disease (ALD). Early-stage ALD exhibits dyshomeostasis of zinc. We investigated the role of zinc deficiency in gut-barrier dysfunction, proinflammatory response, hepatocyte injury, and death, as well as potential sex differences in AUD patients. METHODS: Thirty-nine male and female AUD patients were grouped by normal [≥71 µg/dL (Group 1, number (n) = 26)] and low [<71 µg/dL (Group 2, n = 13)] serum zinc levels. Demographics, alcohol intake markers [Lifetime Drinking History (LTDH), heavy drinking days in the past 90-days (HDD90), total drinks in the past 90-days (TD90), number of drinking days in the past 90-days (NDD90), average drinks per day in the past 90 days (AvgDPD90)] were collected. Blood samples were tested for complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation markers, gut-barrier dysfunction markers, cytokines, and hepatocyte death markers. RESULTS: Group 2 females exhibited lower LTDH than Group 2 males (p = 0.028), but higher recent drinking. Aspartate transaminase: alanine transaminase (AST:ALT) ratio was higher (p = 0.049) in Group 2 males compared to Group 1 males. Overall, Group 2 showed threefold higher interleukin 8 (IL-8) levels than Group 1 (p = 0.92); these were sevenfold higher in Group 2 females than Group 1 females. Group 2 females also had higher K18M65, but lower K18M30 than Group 1 females. Necrotic type of cell death (K18M65) was well-described only in Group 2 by the arrangement of lipopolysaccharide (LPS), soluble cluster of differentiation 14 (sCD14), and tumor necrosis factor alpha (TNF-α) (R2 = 0.633, p = 0.037). CONCLUSION: Our findings demonstrated the role of the gut-immune-liver axis in describing hepatocyte injury and death in zinc-deficient AUD patients. These patients represented an arrangement of gut-barrier dysfunction and an exacerbated immune response. Shift in the cell-death mechanism from apoptosis in zinc-replete females to necrosis in zinc-deficient females suggests a subclinical to clinical transition of ALD associated with zinc status.

Severe Drug-Induced Liver Injury Due to Self-administration of the Veterinary Anthelmintic Medication, Fenbendazole.

Fenbendazole is an anthelmintic agent approved for veterinary applications. Even though it is not approved by the US Food and Drug Administration for human use, such use appears to be increasing due to the popularization of fenbendazole's potential anticancer effects by social media. We describe the first case of histologically confirmed severe drug-induced liver injury, hepatocellular pattern, associated with the self-administration of fenbendazole in a 67-year-old woman who presented with 2 weeks of jaundice. Liver function tests normalized in 3 months after the cessation of fenbendazole.

Evaluation of genetic polymorphism of CYP3A5 in normal healthy participants from western India - A cross-sectional study.

BACKGROUND: CYP3A5 enzymes belong to the phase I Group of drug-metabolizing enzymes, which are involved in the metabolism of 50% of the drugs. Participants with CYP3A5 genotype: CYP3A5 *1/*1 are fast metabolizers of drugs and hence will require higher dosing. Whereas those with CYP3A5 * 3/*3 are poor metabolizers of drugs and will require a lower dose to achieve target drug concentration in the blood and those with CYP3A5 * 1/*3 have intermediate drug metabolizing activity. Pharmacogenetic evaluation may improve disease outcomes by maximizing the efficacy and minimizing the toxicity of drugs in patients. MATERIALS AND METHODS: This is a single-center cross-sectional study conducted in the year 2018-2019 to study the population prevalence of genetic polymorphisms of CYP3A5 in healthy participants from western India. Eligible participants willing to give written, informed consent were enrolled in the study. Subsequently, 2 ml venous blood was collected the deoxyribonucleic acid was extracted and then stored at ‒20°C. Genotyping was done by a polymerase chain reaction and restriction fragment length polymorphism. RESULTS: A total of 400 participants with a median age of 22 years (range: 18-58 years) were included. Among them, the genotype prevalence for CYP3A5 * 1/*1 was 17% (n = 67/400); CYP3A5 * 1/*3 was 37% (n = 149/400) and that of CYP3A5 * 3/*3 was 46% (184/400). Out of the total 400 healthy participants analyzed, the allele frequency for CYP3A5 * 1 was 35% (142/400) and that of CYP3A5*3 was 65% (259/400). CONCLUSION: The genotype prevalence for CYP3A5 * 3*3 (46%) and the allele frequency for CYP3A5 * 3 (65%) respectively were the highest among the western Indian population.

Extranodal Involvement of the Anorectal Region in an HIV-Positive Patient With Plasmablastic Lymphoma: A Case Report.

Plasmablastic lymphoma (PbL) is a rare type of aggressive B-cell malignancy that has an extremely poor prognosis without chemotherapeutic treatment, requiring a high degree of suspicion for an early and accurate diagnosis. It has been classically described in patients infected with the human immunodeficiency virus (HIV). However, it accounts for only 2.6% of acquired immunodeficiency syndrome (AIDS)-related lymphomas. Extranodal involvement is most commonly seen within the oral cavity (44%). Involvement of the gastrointestinal tract (14%) is rare and can often be confused with other malignancies with plasmablastic features. We present a rare case of PbL in a 55-year-old male with HIV-AIDS (CD4 (cluster of differentiation 4) cell count of 128), who presented for evaluation of incidentally detected multiple liver masses and lytic lesions in the ribs. Further workup revealed evidence of a lesion with increased uptake in the anorectal region with fine needle aspiration (FNA) biopsy identifying the lesion as plasmablastic lymphoma.