The Association of Gut Microbiota with Nonalcoholic Steatohepatitis in Thais.

OBJECTIVES: Nonalcoholic steatohepatitis (NASH) can progress to advanced fibrosis; the link between intestinal bacterial overgrowth and NASH has been proposed. Gut microbiota may promote inflammation and provoke disease progression. We evaluated gut microbiota pattern in NASH and its influencing factors. METHODS: A case-controlled study with sixteen NASH and eight control subjects was done. We performed DNA extraction from stool samples and bacterial 16S rRNA sequencing using MiSeq™. The sequences were clustered into operational taxonomic units using Quantitative Insights Into Microbial Ecology software. We calculated relative abundances, determined alpha diversity, obtained beta diversity by principal coordinate analysis, and conducted the partial least-squares regression model. RESULTS: The relative abundance of Bacteroidetes tended to be higher in NASH group. The Bacteroidetes/Firmicutes (B/F) ratio was significantly elevated in NASH patients. The pattern of gut microbiota in NASH was clearly separated from that of control subjects. Factors influencing the separation of NASH from control subjects were age, diabetes, body mass index, Bacteroidetes phylum, metformin, Actinobacteria, Verrucomicrobia, Thermotogae, and Caldithrix and Bacteroidetes/Firmicutes ratio. CONCLUSIONS: Bacteroidetes phylum (Bacteroides and Prevotella genus) is abundant in NASH subjects, who exhibited an elevated B/F ratio. NASH patients showed a specific pattern of gut microbiota independent of diabetes or metformin use.

Reversal of Proximal Renal Tubular Dysfunction after Nucleotide Analogue Withdrawal in Chronic Hepatitis B.

AIMS: Proximal renal tubular dysfunction (PRTD) is an infrequent complication after nucleotide analogue therapy. We evaluated the outcomes of PRTD and nephrotoxicity after nucleotide analogue withdrawal in chronic hepatitis B (CHB). METHODS: A longitudinal follow-up study was performed in patients with PRTD after nucleotide analogue discontinuation. Serum and urine were collected at baseline and every 3 months for one year. The fractional excretion of phosphate (PO4), uric acid (UA), and potassium and tubular maximal reabsorption rate of PO4 to glomerular filtration rate (TmPO4/GFR) were calculated. Renal losses were defined based on the criteria of substance losses. Subclinical PRTD and overt PRTD were diagnosed when 2 and ≥3 criteria were identified. RESULTS: Eight subclinical and eight overt PRTD patients were enrolled. After nucleotide analogue withdrawal, there were overall improvements in GFR, serum PO4, and UA. Renal loss of PO4, UA, protein, and ß2-microglobulin reduced over time. At one year, complete reversal of PRTD was seen in 13 patients (81.2%). Improvements in PRTD were seen in all but one patient. CONCLUSION: One year after nucleotide analogue withdrawal, PRTD was resolved in most patients. Changes in TmPO4/GFR, urinary protein, and ß2-microglobulin indicate that urinary biomarkers may represent an early sign of PRTD recovery.

Nucleotide Analogue-Related Proximal Renal Tubular Dysfunction during Long-Term Treatment of Chronic Hepatitis B: A Cross-Sectional Study.

Background. There have been few reports of nucleotide analogue-related renal tubular dysfunction (RTD) in CHB patients. We assessed the prevalence and presentation of nucleotide analogue-related proximal RTD. Methods. A cross-sectional study was performed in CHB patients taking nucleotide analogues. Inclusion criteria were patients who were on adefovir or tenofovir as mono- or add-on therapy with lamivudine (LAM) >1 year. Serum and urine were collected. Fractional excretion of phosphate (FEPO4), uric acid (FEUA), and potassium was calculated. Renal losses were defined based on the criteria: protein (24-hour urine protein >150 mg), glucose (glycosuria with normoglycemia), phosphate (FEPO4 >18%), uric acid (FEUA >15%), potassium (renal potassium losses with hypokalemia), and bicarbonate (normal gap acidosis). Subclinical and overt proximal RTD were defined when 2 and ≥3 criteria presented. Results. Ninety-two patients were enrolled. The mean duration of nucleotide analogue taking was 55.1 ± 29.6 months. Proximal RTD was found in 24 (26.1%) patients (subclinical 15 (16.3%) and overt 9 (9.8%)). The severity of RTD was associated with the duration of nucleotide analogue (P = 0.01). Conclusions. The prevalence of proximal RTD in CHB patients taking nucleotide analogues was 26%. The severity of RTD was associated with the treatment duration. Comprehensive testing is necessary for early detecting nucleotide analogue-related nephrotoxicity.

Liver Stiffness Measurement in Psoriasis: Do Metabolic or Disease Factors Play the Important Role?

BACKGROUND: An increased prevalence of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) was reported in psoriasis. NAFLD can progress to nonalcoholic steatohepatitis and fibrosis. Transient elastography (TE) is a noninvasive liver fibrosis assessment. We evaluated the prevalence of significant liver fibrosis or high liver stiffness measurement (LSM) using the LSM cutoff over 7 kPa and its associated factors in psoriatic patients. METHODS: Subjects underwent TE and ultrasonography. Univariate and multivariate analysis were performed for the associated factors. RESULTS: One hundred and sixty-eight patients were recruited. Three patients were excluded due to TE failure. Mean BMI was 24.8 ± 4.7 kg/m(2). NAFLD, metabolic syndrome, and diabetes were seen in 105 (63.6%), 83 (50.3%), and 31 (18.8%) patients. The total cumulative dose of methotrexate over 1.5 g was seen in 39 (23.6%) patients. Mean LSM was 5.3 ± 2.9 kPa. High LSM was found in 18 (11.0%) patients. Waist circumference (OR: 1.24; 95% CI: 1.11-1.38; P = 0.0002), diabetes (OR: 12.70; 95% CI: 1.84-87.70; P = 0.010), and AST (OR: 1.08; 95% CI: 1.02-1.16; P = 0.017) were associated with high LSM. CONCLUSION: 11% of psoriatic patients had significant liver fibrosis by high LSM. Waist circumference, diabetes, and AST level were the independent predictors.

A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury.

BACKGROUND: Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown. We aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury (antiTB-DILI) in patients with tuberculosis. METHODS: A double-blind randomized placebo-controlled trial was performed. Tuberculosis patients were randomly allocated to receive placebo or silymarin. The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4. Antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione and malondialdehyde assays) were assessed. The risks of antiTB-DILI between the two groups were compared. A number need to treat was estimated. RESULTS: A total of 55 out of 70 expected numbers of patients were enrolled. There were 1/27 (3.7%) and 9/28 (32.1%) patients who developed antiTB-DILI in the silymarin and the placebo groups. Risk reduction was 0.28 (0.10, 0.47), i.e., receiving silymarin was 28% at lower risk for antiTB-DILI than placebo. This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients. Median (IQR) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 (15, 415) IU/L and 31.5 (20, 184) IU/L (p = 0.455). The decline of SOD level at week 4 in the silymarin group was less than the placebo group (p < 0.027). CONCLUSIONS: Silymarin reduced the incidence of antiTB-DILI. The benefit of silymarin may be explained from superoxide dismutase restoration. Larger clinical trials are required to confirm the result of our small study [Clinicaltrials.Gov Identifier Nct01800487].

Non-alcoholic fatty liver disease (NAFLD) and significant hepatic fibrosis defined by non-invasive assessment in patients with type 2 diabetes.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), the most common liver problem in diabetes, is a risk factor for liver cancer. Diabetes, high body mass index (BMI) and old age can all contribute to NAFLD progression. Transient elastography (TE) is used for non-invasive fibrosis assessment. OBJECTIVES: To identify the prevalence of NAFLD and significant hepatic fibrosis in diabetic patients and to assess associated factors. MATERIALS AND METHODS: One hundred and forty-one diabetic and 60 normal subjects were screened. Fatty liver was diagnosed when increased hepatic echogenicity and vascular blunting were detected by ultrasonography. Liver stiffness measurement (LSM) representing hepatic fibrosis was assessed by TE. LSM ≥7 kPa was used to define significant hepatic fibrosis. RESULTS: Four cases were excluded due to positive hepatitis B viral markers and failed TE. Diabetic patients had higher BMI, systolic blood pressure, waist circumference and fasting glucose levels than normal subjects. Fatty liver was diagnosed in 82 (60.7%) diabetic patients but in none of the normal group. BMI (OR: 1.31; 95%CI: 1.02-1.69; p=0.038) and alanine aminotransferase (ALT)(OR: 1.14; 95%CI: 1.05-1.23; p=0.002) were associated with NAFLD. Diabetic patients with NAFLD had higher LSM than those without [5.99 (2.4) vs 4.76 (2.7) kPa, p=0.005)]. Significant hepatic fibrosis was more common in diabetic patients than in normal subjects [22 (16.1%) vs 1 (1.7%), p=0.002]. Aspartate aminotransferase (AST)(OR: 1.24; 95%CI: 1.07-1.42; p=0.003) was associated with significant hepatic fibrosis. CONCLUSIONS: Sixty and sixteen percent of diabetic patients were found to have NAFLD and significant hepatic fibrosis. High BMI and ALT levels are the predictors of NAFLD, and elevated AST level is associated with significant hepatic fibrosis.