Background & Aims
How adiposity influences the effect of genetic variants on non‐alcoholic fatty liver disease (NAFLD) in the Asian population remains unclear. We aimed to study the association ...between genetic risk variants and susceptibility/severity of NAFLD in the lean, overweight and obese individuals.
Methods
Nine hundred and four community subjects underwent proton‐magnetic resonance spectroscopy and transient elastography examination. Lean (<23 kg/m2), overweight (23‐24.9 kg/m2) and obesity (≥25 kg/m2) were defined according to the body mass index cut‐offs for Asians. NAFLD was defined as intrahepatic triglycerides ≥5%. PNPLA3, TM6SF2, MBOAT7 and 9 other gene polymorphisms were analysed by rhAMPTM SNP assays.
Results
Five hundred and twenty‐nine (58.5%), 162 (17.9%) and 213 (23.6%) subjects were lean, overweight and obese, respectively. The prevalence of NAFLD was 12.4%, 41.4% and 59.1% in the three groups (P < .001). Amongst those with NAFLD, lean subjects (30.3%) were more likely to carry the PNPLA3 rs738409 GG genotype than overweight (17.9%) and obese subjects (17.4%) (P = .003). Compared with the CC genotype, the GG genotype was associated with the greatest increase in the risk of NAFLD in lean subjects (odds ratio OR 6.04), compared with overweight (OR 3.43, 95% CI 1.06, 11.14) and obese subjects (OR 2.51, 95% CI 0.93, 6.78). Additionally, the TM6SF2 rs58542926 TT genotype was associated with reduced serum triglycerides only in lean subjects. A gene‐BMI effect was not observed for the other gene polymorphisms.
Conclusions
The PNPLA3 rs738409 gene polymorphism has a greater effect on liver fat in Asian lean individuals than in overweight or obese ones.
Serum hepatitis B surface antigen (HBsAg) quantification has been suggested to reflect the concentration of covalently closed circular DNA in the liver. We aimed to investigate the HBsAg levels at ...different stages of chronic hepatitis B and the changes in HBsAg level during the natural progression of disease. One hundred seventeen untreated patients with chronic hepatitis B were studied with longitudinal follow‐up for 99 ± 16 months. HBsAg quantification was performed at the first visit, the last visit, and three visits at each quartile during the follow‐up. At the first visit, HBsAg level was higher among patients who were hepatitis B e antigen (HBeAg)‐positive (N = 49) than those who were HBeAg‐negative (N = 68) (4.01 ± 0.91 log IU/mL versus 2.73 ± 1.25 log IU/mL, P < 0.001). HBsAg level was persistently high at approximately 5 log IU/mL among patients in the immune tolerance phase (N = 7). The HBsAg levels among patients with HBeAg‐positive active disease (N = 25) or sustained HBeAg seroconversion (N = 17) were comparable at approximately 3‐4 log IU/mL. The HBsAg levels among patients who were HBeAg‐negative tended to be higher among patients with active (N = 46) than those with inactive disease (N = 22). The median HBsAg levels decreased in HBeAg‐negative patients with active and inactive disease by 0.041 log IU/mL/year and 0.043 log IU/mL/year, respectively. Twenty‐two (17%) patients had HBsAg reduction >1 log IU/mL at the last visit; most of them showed reduced hepatitis B virus DNA, and eight had HBsAg loss. Conclusion: HBsAg remained stable in HBeAg‐positive patients and tended to reduce slowly in HBeAg‐negative patients. Reduction of HBsAg for >1 log IU/mL could reflect improved immune control. (HEPATOLOGY 2010)
Objective
Multiple trials have demonstrated the metabolic effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors in patients regardless of diabetes status, and recent trials have been conducted ...on the combined sodium/glucose cotransporter 1 and sodium/glucose cotransporter 2 (SGLT1/SGLT2) inhibitors. Therefore, a meta‐analysis was conducted to investigate the weight reduction effects and dose‐response relationship of SGLT inhibitors and to assess the relative efficacy of SGLT1/SGLT2 inhibitors.
Methods
Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched on November 21, 2020, for articles published from January 1, 2000, up to November 21, 2020.
Results
In total, 116 randomized‐controlled trials were included, with a combined cohort of 98,497 patients. Overall, patients had a mean weight reduction of −1.79 kg (95% CI: −1.93 to −1.66, p < 0.001) compared with placebo. This effect was observed across diabetes status, duration of follow‐up, various comorbidities, and all SGLT drug types. Mean BMI changes were −0.71 kg/m2 (95% CI: −0.94 to −0.47, p < 0.001) compared with placebo. Canagliflozin, empagliflozin, sotagliflozin, and licogliflozin showed a dose‐response relationship for mean weight change. Compared with SGLT2 inhibitors, SGLT1/SGLT2 inhibitors had a significantly larger reduction in weight.
Conclusions
SGLT inhibitors demonstrated weight reduction benefits in this meta‐analysis. Further studies are needed to clarify their role in weight management.
The human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH). The relationship ...between microbiota changes and changes in hepatic steatosis was also studied.
Fecal microbiota of histology-proven NASH patients and healthy controls was analyzed by 16S ribosomal RNA pyrosequencing. NASH patients were from a previously reported randomized trial on probiotic treatment. Proton-magnetic resonance spectroscopy was performed to monitor changes in intrahepatic triglyceride content (IHTG).
A total of 420,344 16S sequences with acceptable quality were obtained from 16 NASH patients and 22 controls. NASH patients had lower fecal abundance of Faecalibacterium and Anaerosporobacter but higher abundance of Parabacteroides and Allisonella. Partial least-square discriminant analysis yielded a model of 10 genera that discriminated NASH patients from controls. At month 6, 6 of 7 patients in the probiotic group and 4 of 9 patients in the usual care group had improvement in IHTG (P=0.15). Improvement in IHTG was associated with a reduction in the abundance of Firmicutes (R(2)=0.4820, P=0.0028) and increase in Bacteroidetes (R(2)=0.4366, P=0.0053). This was accompanied by corresponding changes at the class, order and genus levels. In contrast, bacterial biodiversity did not differ between NASH patients and controls, and did not change with probiotic treatment.
NASH patients have fecal dysbiosis, and changes in microbiota correlate with improvement in hepatic steatosis. Further studies are required to investigate the mechanism underlying the interaction between gut microbes and the liver.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims: Our aims were to study the virologic, histologic, and clinical outcome in chronic hepatitis B (CHB) patients with hepatitis B surface antigen (HBsAg) seroclearance. Methods: We ...determined the age of HBsAg seroclearance that is associated with a lower risk for hepatocellular carcinoma (HCC) in 298 CHB patients (median follow-up, 108 months). The following virologic and histologic features were also determined: liver stiffness (n = 229), liver histology, serum HBV DNA levels over time (n = 265), intrahepatic HBV DNA with covalently closed circular DNA (cccDNA) levels, and messenger RNA (mRNA) expression. Results: The median age of HBsAg seroclearance was 49.6 years. Seven (2.4%) patients developed HCC. Cumulative risk for HCC was higher in patients with HBsAg seroclearance at ages ≥50 years compared with those with HBsAg seroclearance at ages <50 ( P = .004) years. Of these 2 groups of patients, 29.5% and 7.9%, respectively, had significant fibrosis by liver stiffness measurement ( P = .001), and 15.4% of patients had mild histologic fibrosis. Intrahepatic total HBV DNA and cccDNA were detected in 100% and 79.3% of patients, respectively. All patients had undetectable surface and precore/pregenomic RNA transcripts. One (9.1%) patient had X mRNA expression. Serum HBV DNA were detectable in 13.4%, 6.1%, and 3.7% of patients within 1 year and 5–10 and >10 years after HBsAg seroclearance, respectively, and 82.1% patients had persistently normal alanine aminotransferase levels. Conclusions: HBV persisted at low replicative and transcriptional levels after HBsAg seroclearance. HBsAg seroclearance at age <50 years was associated with a lower risk for the development of HCC.
Alpha‐fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) surveillance, which is criticized as neither sensitive nor specific in active hepatitis and liver ...cirrhosis. The aim of this study was to determine the performance of AFP as a tumor marker for HCC in entecavir‐treated patients with chronic hepatitis B (CHB). This was a retrospective‐prospective cohort study of 1,531 entecavir‐treated patients under regular HCC surveillance with AFP and ultrasonography. Mean age was 52 ± 12 years; 1,099 (72%) patients were male and 332 (21.7%) had clinical evidence of cirrhosis. At a mean follow‐up of 51 ± 13 months, 57 (2.9%) patients developed HCC (median size: 3.3 cm). AFP fluctuated with alanine aminotransferase (ALT) and peaked at the time of starting entecavir, then gradually decreased after. AFP started to increase 6 months before the diagnosis of HCC. The receiver operator characteristic curve (AUROC) of AFP was highest at the time of HCC diagnosis (0.85; 95% confidence interval CI: 0.73‐0.98) and remained satisfactory at 3 (0.82; 95% CI: 0.73‐0.91) and 6 months (0.79; 95% CI: 0.69‐0.89) before the diagnosis. Using the conventional AFP cut‐off (20 μg/L) at month 0, the sensitivity and specificity to diagnose HCC were 38.6% and 98.9%, respectively. Adopting the lower cut‐off value (6 μg/L) of AFP level at month 0, sensitivity was increased to 80.7%, whereas specificity was decreased to 80.4%. Conclusion: On‐treatment AFP is a specific tumor marker for HCC in CHB patients receiving entecavir therapy. Adopting a lower cut‐off value of AFP level at 6 μg/L would significantly increase the sensitivity for HCC detection. (Hepatology 2014;59:986–995)
Background & Aims Little is known about the validity of hepatocellular carcinoma (HCC) risk scores derived from treatment-naïve patients with chronic hepatitis B for patients treated with entecavir. ...Methods We performed a retrospective-prospective cohort study of 1531 patients with chronic hepatitis B (age, 51 ± 12 years; 1099 male; 332 with clinical cirrhosis) who were treated with entecavir 0.5 mg daily for at least 12 months at Prince of Wales Hospital in Hong Kong from December 2005 to August 2012. The patients were assessed once every 3 to 6 months for symptoms, drug history, and adherence; blood samples were collected for biochemical analyses. We validated 3 HCC risk scores (CU-HCC, GAG-HCC, and REACH-B scores) based on data collected when patients began treatment with entecavir and 2 years later. Results After 42 ± 13 months of follow-up, 47 patients (2.9%) developed HCC. The 5-year cumulative incidence of HCC was 4.3% (95% confidence interval CI, 3.6%–5.0%). Older age, presence of cirrhosis, and virologic remission after 24 months or more of therapy were independently associated with HCC in the entire cohort; advanced age and hypoalbuminemia were associated with HCC in patients without cirrhosis. The area under the receiver operating characteristic curves (AUCs) for baseline CU-HCC, GAG-HCC, and REACH-B scores for HCC were 0.80 (95% CI, 0.75–0.86), 0.76 (95% CI, 0.70–0.82), and 0.71 (95% CI, 0.62–0.81), respectively; the time-dependent AUCs 1 to 4 years after patients started treatment were comparable to those at baseline. The cutoff value of the baseline CU-HCC score identified patients who would develop HCC with 93.6% sensitivity and 47.8% specificity, the baseline GAG-HCC score with 55.3% sensitivity and 78.9% specificity, and the baseline REACH-B score with 95.2% sensitivity and 16.5% specificity. Compared with patients with CU-HCC scores <5 at baseline, those with CU-HCC scores that either decreased from ≥5 to <5 or remained ≥5 had a higher risk of HCC (5-year cumulative incidences, 0% vs 3.9% and 7.3%; P = .002 and P < .001, respectively). Conclusions The CU-HCC, GAG-HCC, and REACH-B HCC risk scores accurately predict which patients with chronic hepatitis B treated with entecavir will develop HCC.
Abstract Background/Aims To determine whether gender, age, hepatitis B virus genotype, core promoter and precore mutations, HBeAg/ anti-HBe status, HBV DNA, ALT levels and cirrhosis on presentation ...were independent risk factors and derive a novel risk score for the development of HCC. Methods CHB patients (820) were followed up (mean duration 76.8 months) for the occurrence of HCC. Results The 5- and 10-year prevalence of HCC were 4.4% and 6.3%, respectively. Cox regression analysis showed that male gender ( p = 0.025, RR 2.98), increasing age ( p < 0.001, RR 1.07), higher HBV DNA levels ( p = 0.02, RR 1.28), core promoter mutations ( p = 0.007, RR 3.66), and presence of cirrhosis ( p < 0.001, RR 7.31) were independent risks for the development of HCC. A risk score was derived and validated with sensitivity > 84% and specificity > 76% to predict the 5- and 10- year risks for the development of HCC. The AUC for the 5- and 10-year prediction were 0.88 and 0.89, respectively. Conclusions The risk score, based on age, gender, HBV DNA levels, core promoter mutations and cirrhosis, can estimate the chance of development of HCC in 5 and 10 years after presentation. It can be used to identify high-risk CHB patients for treatment and screening of HCC.
Although the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by ...deranged parenchymal liver enzymes. Furthermore, the severity of liver damage has been shown to correlate with higher mortality. Overall, the mechanism behind the liver injury remains unclear. We showed in this study that intra-hepatic bile duct cells could be grown using a human liver organoid platform. The cholangiocytes were not only susceptible to SARS-CoV-2 infection, they also supported efficient viral replication. We also showed that SARS-CoV-2 replication was much higher than SARS-CoV. Our findings suggested direct cytopathic viral damage being a mechanism for SARS-CoV-2 liver injury.
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