Liver Biochemistries In Patients Research Articles

Factors associated with treatment responses to pioglitazone in patients with steatotic liver disease: A 3-year prospective cohort study.

The response rate to pioglitazone and the predictive factors for its effects on improving liver biochemistry in patients with steatotic liver disease (SLD) remain elusive, so we aimed to investigate these issues. A 3-year prospective cohort study of 126 Taiwanese patients with SLD treated with pioglitazone (15-30 mg/day) was conducted. Phospholipase domain-containing protein 3 I148M rs738409, methylenetetrahydrofolate reductase rs1801133, aldehyde dehydrogenase 2 (ALDH2) rs671 and lipoprotein lipase rs10099160 single nucleotide polymorphisms were assessed in the patients. Of 126 patients, 78 (61.9%) were men, and the mean and median ages were 54.3 and 56.5 years, respectively. Pioglitazone responders were defined as those with decreased alanine aminotransferase (ALT) levels at 6 months post-treatment, and 105 (83.3%) patients were responders. Compared with non-responders, responders were more frequently women and had higher baseline ALT levels. The proportion of patients with the ALDH2 rs671 GG genotype was lower among responders (38.6% vs. 66.6%, p = .028). Female sex [odds ratio (OR): 4.514, p = .023] and baseline ALT level (OR: 1.015, p = .046; cut-off level: ≥82 U/L) were associated with pioglitazone response. Among responders, the liver biochemistry and homeostasis model assessment of insulin resistance improved from 6 to 24 months post-treatment. The total cholesterol levels decreased within 6 months, while increases in high-density lipoprotein cholesterol levels and decreases in triglyceride levels and fibrosis-4 scores were noted only at 24 months post-treatment. The 2-year cumulative incidences of cardiovascular events, cancers and hepatic events were similar between responders and non-responders. Regarding liver biochemistry, over 80% of Taiwanese patients with SLD had a pioglitazone response, which was positively associated with female sex and baseline ALT levels. Insulin resistance improved as early as 6 months post-treatment, while liver fibrosis improvement was not observed until 24 months post-treatment. The link between the pioglitazone response and the ALDH2 genotype warrants further investigation.

Efficacy and Safety of Bezafibrate Alone or in Combination with Ursodeoxycholic Acid in Primary Biliary Cholangitis: Systematic Review and Meta-Analysis.

Bezafibrate (BZF) alone or in combination with ursodeoxycholic acid (UDCA) has been used to slow disease progression in patients with primary biliary cholangitis (PBC). We performed a systematic review and meta-analysis to assess the efficacy and harms of BZF monotherapy or combination therapy. We performed a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception until January 2020, for randomized controlled clinical trials assessing BZF + UDCA versus UDCA monotherapy or BZF monotherapy versus UDCA monotherapy in PBC patients. Additionally, we systematically evaluated data on harms using seven observational studies. Pooled effect estimates were calculated for the outcomes of interest. The certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). We identified 7 randomized controlled trials with a total of 279 participants. Comparing BZF + UDCA to UDCA alone, a clinically significant improvement was observed in serum ALP with a mean difference (MD) of - 159.04 U/L (95% CI - 186.45 to - 131.62) and a reduction in gamma-glutamyltransferase (GGT) (MD - 106.94IU/L; 95% CI - 151.99 to - 61.89), but not in total bilirubin (TB) or IgM levels. A statistically significant reduction in ALP levels was also noticed with BZF monotherapy compared to UDCA monotherapy. The effect of BZF + UDCA versus UDCA on mortality remains unclear. Across 5 observational studies including 106 patients, one death was reported due to advanced liver disease in an incomplete responder getting treatment with BZF + UDCA. Analysis of observational studies demonstrated improvement in pruritus intensity with BZF. Use of BZF alone or in combination with UDCA improved liver biochemistries in patients with PBC, but its effect on mortality, liver-related complications or quality of life remains unknown.

Clinical Features of Patients Infected With Coronavirus Disease 2019 With Elevated Liver Biochemistries: A Multicenter, Retrospective Study.

Background and AimsIn December 2019, an outbreak of coronavirus disease 2019 (COVID‐19) emerged in Wuhan, China. Although it has been reported that some patients with COVID‐19 showed elevated liver biochemistries, there are few studies regarding the clinical features and prognosis of these patients.Approach and ResultsIn this multicenter, retrospective study, we collected data on laboratory‐confirmed patients with COVID‐19 from three hospitals in Wuhan, China, who died or were discharged between February 1, 2020, and February 20, 2020. Data on demographics, comorbidities, clinical symptoms, laboratory examinations on admission, complications, treatment, and outcome were collected. A total of 482 patients were enrolled in this study. Of those, 142 (29.5%) patients showed abnormal liver biochemistries on admission, and patients with elevated alanine aminotransferase, aspartate aminotransferase (AST), and total bilirubin (TBIL) accounted for 67.6%, 69.0%, and 16.2%, respectively. Those with abnormal liver biochemistries showed higher percentages of severe cases and comorbidities and were more likely to have dyspnea, chest distress or pain, and increased hemoglobin (Hb) on admission. Higher rates of complications and mortality and worse recovery when discharged were observed in patients with abnormal AST or TBIL. Multivariable regression analysis showed that chest distress or pain (odds ratio [OR], 1.765; P = 0.018), dyspnea (OR, 2.495; P = 0.001), elevated C‐reactive protein level (OR, 1.007; P = 0.008), elevated white blood count (OR, 1.139; P = 0.013), and elevated Hb concentration (OR, 1.024; P = 0.001) were independent factors associated with elevated liver biochemistries in patients with COVID‐19.ConclusionsElevated liver biochemistries were common in patients with COVID‐19. Patients with hypoxia or severe inflammation are more likely to experience increased liver biochemistries on admission. Those with abnormal AST or TBIL on admission are more likely to suffer from severe complications and death.

Spontaneous Fluctuations in Liver Biochemistries in Patients with Compensated NASH Cirrhosis: Implications for Drug Hepatotoxicity Monitoring.

Patients with cirrhosis may have spontaneous fluctuations in liver enzymes, which may confound detection of drug-induced liver injury (DILI), but these fluctuations have not been described. We sought to quantify spontaneous liver enzyme abnormalities in patients with cirrhosis due to nonalcoholic steatohepatitis (NASH) enrolled in clinical trials. We examined the laboratory values of patients with compensated cirrhosis randomized to placebo in two clinical trials for NASH. Patients in one study were followed every 13 weeks up to week 57; patients in the other study were followed every 4 weeks up to week 120. In total, 53 and 85 patients were randomized to placebo in the trials. Baseline alanine aminotransferase (ALT) was greater than the laboratory upper limit of normal (ULN) in 53% and 49% of participants, aspartate aminotransferase (AST) was > ULN in 49% and 59%, alkaline phosphatase was > ULN in 36% and 27%, and bilirubin was >ULN in 13% and 19%. During follow-up, ALT increased to 2× baseline in 8% and 15%, AST increased to 2× baseline in 6% and 21%, and bilirubin increased to 2× baseline in 9% and 18%. Alkaline phosphatase did not increase to 2× baseline for any patient. The maximum ALT was 3× ULN in 9% and 12%. ALT increased to 3× baseline in three patients and to 5× ULN in two patients. No patients had elevations consistent with Hy's law. The maximum ALT for patients with abnormal baseline values was higher [median 48 U/L (range 34-299) and 56 U/L (47-85)] than for those with normal baseline values [median 26.5 U/L (range 18-33) and 29 U/L (25.5-30.5)] in both studies, respectively, with p < 0.001. Spontaneous liver enzyme abnormalities are common in patients with NASH cirrhosis in clinical trials, and these abnormalities rarely met criteria for DILI suspicion. Further work to better define these abnormalities and continued vigilance to detect DILI in this population is needed.

A Cross-Sectional Study of the Relationship between Serum Creatine Kinase and Liver Biochemistry in Patients with Rhabdomyolysis

Abnormal liver function tests are commonly observed with rhabdomyolysis, but the nature of this association is not fully defined. This study aims to determine the functional relationship between serum creatine kinase, as a marker of rhabdomyolysis severity, and liver biochemistry. We used linear regression to model the relationship between liver biochemistry and peak serum creatine kinase. A total of 528 patients with a median age of 74 years were included. The distribution of creatine kinase, bilirubin, alkaline phosphatase, alanine aminotransferase, and γ-glutamyl transferase were significantly skewed, and these variables were log-transformed prior to regression. There was a positive linear correlation between log-alanine aminotransferase and log-creatine kinase. In the multiple regression analysis, log-creatine kinase, age, acute kidney injury stage, and chronic liver disease were independently associated with log-alanine aminotransferase. This model explained 46% of the variance of log-alanine aminotransferase. We found no correlation between the log-creatine kinase and the log-bilirubin, log-alkaline phosphatase, or log-γ-glutamyl transferase. Serum alanine aminotransferase was not associated with inpatient mortality but a higher creatine kinase-alanine aminotransferase ratio was associated with lower odds of mortality. In conclusion, an isolated elevation in alanine aminotransferase can occur in rhabdomyolysis, and it may be possible to anticipate the level of increase based on the peak creatine kinase.

A Randomized, Controlled Trial of Vitamin D Supplementation on Cardiovascular Risk Factors, Hormones, and Liver Markers in Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) increases the risk of metabolic syndrome and non-alcoholic-fatty-liver disease (NAFLD). Vitamin D supplementation may exert positive effects on liver biochemistry in patients with NAFLD; however, its effects on PCOS are unknown. This randomized, double-blind, placebo-controlled study explored the effect of vitamin D supplementation on cardiovascular risk factors (high-sensitivity C-reactive protein (hs-CRP), weight, body mass index (BMI), lipid profile, glucose levels, insulin levels, the homeostatic model assessment-insulin resistance (HOMA-IR), hormones (free androgen index (FAI), testosterone, sex hormone binding globulin (SHBG), and liver markers (alanine aminotransferase (ALT), hyaluronic acid (HA), N-terminal pro-peptide of type III procollagen (PIIINP), tissue inhibitor of metallo-proteinases-1 (TIMP-1), and the enhanced liver fibrosis (ELF) score). Forty women with PCOS were recruited and randomized to vitamin D (3200 IU) or placebo daily for 3 months. All outcomes were measured at baseline and 3 months follow-up (FU). Greater increases in vitamin D levels were shown in the supplementation group (vitamin D, baseline: 25.6 ± 11.4 nmol/L, FU: 90.4 ± 19.5 nmol/L vs. placebo, baseline: 30.9 ± 11.1 nmol/L, FU: 47.6 ± 20.5 nmol/L, p < 0.001). Between groups comparisons (% baseline change) revealed significant differences in ALT (p = 0.042) and a weak effect indicating a greater reduction in the HOMA-IR in the vitamin D group (p = 0.051). No further between group differences were seen in other cardiovascular risk factor, liver markers, or hormones. This study supports beneficial effects of vitamin D supplementation on liver markers and modest improvements in insulin sensitivity in vitamin D deficient women with PCOS.

Effects of Bezafibrate on Outcome and Pruritus in Primary Biliary Cholangitis With Suboptimal Ursodeoxycholic Acid Response.

Adding fibrates improves liver biochemistries in patients with primary biliary cholangitis (PBC) and suboptimal response to ursodeoxycholic acid (UDCA). As there are no consistent data regarding the course and outcome, we have assessed the effects of the combined treatment with UDCA and bezafibrate on a long-term basis. A total of 48 patients (45 female) with PBC treated with UDCA and alkaline phosphatase (ALP) above 1.5 times upper normal levels (× UNL) were treated with bezafibrate (400 mg/day) plus UDCA (13-16 mg/kg/day). Changes in clinical features, liver biochemistries, and prognosis after therapy were assessed, as well as pruritus, using a visual analog scale (43 patients) and the 5-D descriptive pruritus scale. After a median of 38 months, 26 patients (54%) had normalized ALP. In these patients, jaundice, pruritus, and liver stiffness was lower, and age was higher than in patients who remained with elevated ALP. Biochemical improvement was less prominent in patients without ALP normalization. Five of these patients (23%) developed events of disease progression: 1 died, 3 were transplanted, and 1 developed hepatocellular carcinoma. Partial or complete itching relief was reported in all but one case with pruritus. Itching recurrence or worsening was observed after bezafibrate discontinuation. The long-term treatment with UDCA and bezafibrate results in excellent response, and is associated with a complete or partial itching relief. Incomplete ALP normalization was observed in patients with advanced disease who remained at risk for developing severe events. The combined treatment is mainly effective in patients with lower fibrosis and severity of cholestasis.

Sa1950 - Vedolizumab is Safe and Effective for IBD, but has no Effect on Liver Biochemistry in Patients with Concurrent PSC

Sa1950 - Vedolizumab is Safe and Effective for IBD, but has no Effect on Liver Biochemistry in Patients with Concurrent PSC

P410 Vedolizumab is safe and effective for IBD, but has no effect on liver biochemistry in patients with concurrent PSC

Background: Blocking of lymphocyte trafficking is a potential mechanism to alter the disease course of primary sclerosing cholangitis (PSC). We studied the effect of the selective α4β7 integrin antibody, vedolizumab, on liver biochemistry and inflammatory bowel disease (IBD) activity in patients with IBD and PSC (IBD-PSC). Methods: We reviewed electronic medical records of adult patients who had an established diagnosis of IBD-PSC from five tertiary centers. We assessed baseline patient and disease characteristics and treatment exposures. The primary outcome was change in serum alkaline phosphatase at weeks 14 and 30. Secondary outcomes included changes in other liver biochemistries, the Mayo Risk Score for PSC and IBD clinical and endoscopic remission. We also performed a safety analysis for the development of adverse events including liver-related complications. Results: We identified 34 patients with IBD-PSC. Nine (26%) had a history of orthotopic liver transplant, 7 were on stable doses of ursodeoxycholic acid (UDCA) and 2 patients commenced UDCA during the study period. Median follow-up was 9 (IQR: 7–16) months; 28 (92%) had at least 6 months of clinical follow-up. Serum alkaline phosphatase activities did not significantly decrease with vedolizumab therapy (median 268 (IQR: 105–551) IU/L at baseline versus 249 (IQR: 183–634) IU/L, p=0.9899 at week 30). Of the 18 patients with an abnormal alkaline phosphatase at baseline (>120IU/L), 11 (61%) had improvement with treatment. In these patients, alkaline phosphatase trended down from 475 IU/L (IQR: 241–757) at baseline to 283 IU/L (IQR: 207–658), p=0.267 at week 30 but none of these normalized (Figure 1). Median alkaline phosphatase changes remained similar when patients exposed to UDCA were excluded. Of the 8 patients (31%) with normal alkaline phosphatase at baseline, 4 (50%) had a subsequent increase to abnormal levels by week 30, from a baseline median of 98 IU/L (IQR: 77–102) to 146 IU/L (IQR: 90–203), p=0.036 at week 30 (Figure 2). No significant changes in other liver biochemistries or the Mayo PSC Risk Score were demonstrated at week 30. 55% of Crohn's disease and 21% of ulcerative colitis patients achieved clinical remission at week 30. Seven patients (21%) ceased vedolizumab therapy; one for a deterioration in liver biochemistry thought to be a drug reaction and six for IBD primary non-response. Two patients developed ascending cholangitis but continued vedolizumab. Conclusions: Vedolizumab therapy in patients with IBD-PSC has little overall effect on liver biochemistry, but is safe and does improve IBD clinical activity. Treatment earlier in the disease course of PSC and assessment of longer-term exposure of lymphocyte trafficking blockade in IBD-PSC remains of interest.

FRI-369 - S-adenosyl-L-methionine improves quality of life and liver biochemistry in patients with primary biliary cholangitis: a prospective, single centre study

FRI-369 - S-adenosyl-L-methionine improves quality of life and liver biochemistry in patients with primary biliary cholangitis: a prospective, single centre study

Variation in Liver Biochemistries in Patients with Decompensated Cirrhosis: Implications for Assessing Drug-Induced Liver Injury in Clinical Trials

Background Current approaches to detection of drug-induced liver injury (DILI) are generally based on changes from normal in biochemical liver tests. However, limited information is available regarding the proportion of patients with normal versus abnormal biochemical tests, the expected temporal pattern of biochemical abnormalities, or the applicability of current approaches to DILI detection for patients with pre-existing liver disease.

Su1264 Prevalence, Causes and Impact of Abnormal Liver Biochemistries in Patients With Inflammatory Bowel Disease

Su1264 Prevalence, Causes and Impact of Abnormal Liver Biochemistries in Patients With Inflammatory Bowel Disease

P206 - Which patient population profits best from a high dose, once daily treatment with 3.0g mesalazine for maintaining clinical remission in ulcerative colitis? A subgroup analysis of a double-blind, double-dummy, randomised, controlled, dose-ranging study

of 6 patients (50%) completed the studies (1 CHARM, 2 GAIN). Reasons for discontinuation included PSC-related pancreatitis (1 patient), CD flare (1 patient), and total body rash (1 patient). CDAI responses at last visit were 50% (3/6) remission, 67% (4/6) CR-100, and 83% (5/6) CR-70. Half had abnormal liver biochemistry at baseline, with no notable change or worsening of liver biochemistry, either acutely or during longer exposure to adalimumab. Conclusions: In this small cohort of PSC patients, adalimumab was well-tolerated, without changes in liver biochemistry in patients with concomitant CD treated during CHARM and GAIN. For the 3 patients who completed the trials, adalimumab sustained remission and/or response, with no appreciable difference in the efficacy rates vs. those for patients without PSC.

Moexipril in Patients with Non-Alcoholic Fatty Liver Disease

Purpose: The blockade of angiotensin II synthesis attenuates hepatic fibrosis in different experimental models of chronic liver injury. We aimed to determine the safety and efficacy of moexipril, an angiotensin-converting enzyme (ACE) inhibitor, on liver biochemistries in patients with non-alcoholic fatty liver disease (NAFLD). Methods: Four patients with biopsy proven NAFLD were enrolled. Oral moexipril 15 mg/day was administered for 1 year to three patients. Results: No significant changes in serum alkaline phosphatase (96 ± 32 vs. 93 ± 6 U/L, P= 0.9), total bilirubin (1.5 ± 0.9 vs. 2.1 ± 0.3 mg/dl, P= 0.7), aspartate aminotransferase (48 ± 9 vs. 44 ± 23 U/L, P= 0.4), albumin (4.4 ± 0.3 vs. 4.2 ± 0.6 g/dl, P= 0.9) were noted after 1 year of treatment. One of the 3 patients who received medication withdrew from the study at 6 months. No major adverse reactions were observed, but 2 out of 3 patients complained of increased fatigue. Conclusion: Moexipril was not clinically beneficial to patients with NAFLD.

The effect of cholestyramine on gallbladder motility and liver biochemistry in patients with primary sclerosing cholangitis (PSC).

s of the Netherlands Society of Gastroenterology and the Netherlands Society of Hepatology: Spring Meeting, 15–16 March 2001

The effect of cholestyramlne on gallbladder motillity and liver biochemistry in patients with primary sclerosing cholangitis (PSC)

The effect of cholestyramlne on gallbladder motillity and liver biochemistry in patients with primary sclerosing cholangitis (PSC)

The effect of cholestyramlne on gallbladder motillity and liver biochemistry in patients with primary sclerosing cholangitis (PSC)

Background: The prevalence of cholesterol gallstones has substantially increased in the last century, especially in affluent countries. Genetic and environmental factors have been implicated in the pathogenesis of gallstones. Yet, the role of many specific environmental factors remains unclear or controversial. Aim: To study the role of diet and lifestyle habits in asymptomatic gallstone disease. Methods: Subjects with asymptomatic, gallbladder stones detected by ultrasonography (US) were enrolled. A total of 103 newly diagnosed patients (75 females, 28 males) were matched by age, sex and ethnic origin to 103 gallstone-free subjects. All subjects underwent abdominal US and were extensively interviewed on their dietary habits using a Food Frequency Questionnaire, and on their lifestyle habits. Major food items were analyzed for their phospholipid content and included in the food composition tables. Results: The paired analysis revealed the following dietary risk factors for the development of gallstones: Total fat intake (p = 0.038), especially fat of animal origin (p = 0.001), total protein (p<O.OOl), protein of animal origin (p<O,OOl), chicken (p<O.O01) and phosphatidylsedne (p=0.016). The following factors were found to be protective: Dietary fiber (p = 0.009), starch (p = 0.03), zinc (p = 0.028) and alcohol (p = 0.039). In addition, high BMI (p<O.O01), serum cholesterol (p=O.042) and triglyceddes (p=O.OO8), marital status (p=O.OOf) and a family history of gallstones (p<O.O05) were found to correlate with the presence of gallstones. Conclusions: The results of the study indicate that nutritional factors are strongly associated with gallstone disease, as risk factors as well as protective factors. The significant association with fat and protein of animal origin, suggests that foods, of this origin should be avoided by subjects with any additional risk of gallstone development.