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Abstract Background Cytoplasmic inclusion bodies within hepatocytes may have different etiologies, including the Endoplasmic Reticulum Storage Diseases (ERSDs). ERSD is a pathological condition characterized by abnormal accumulation of proteins destined for secretion in the endoplasmic reticulum of hepatocytes; it may be congenital (primary) or acquired (secondary). Fibrinogen storage disease is a form of ERSD. Case Presentation We present a case of fibrinogen storage disease secondary to estrogen replacement therapy. Its causal relationship to the drug is shown by histological, immunohistochemical and ultrastructural studies of paired liver biopsies obtained during and after the drug therapy. Conclusion The liver biopsies of patients with idiopathic liver enzyme abnormalities should be carefully evaluated for cytoplasmic inclusion bodies and, although rare, fibrinogen deposits.

Objective: The carbon-14 ((14)C) urea breath test (UBT) is a reliable and noninvasive technique for the diagnosis of Helicobacter pylori (HP) infection. The diagnostic performance of a new practical and low dose (14)C UBT system (Heliprobe, Stockholm, Sweden) was compared with those of other diagnostic tests, namely, rapid urease test (RUT), histopathology, and DNA detection using polymerase chain reaction (PCR). Methods: Eighty-nine patients (mean age = 45 +/- 13, 30 men) with dyspeptic complaints who underwent an endoscopic procedure were studied. Biopsy specimens acquired during the procedure were subjected to RUT, histopathological examination using hematoxylin and eosin (HP-HE) and PCR. All patients underwent UBT using the Heliprobe system on a different day. The gold standard for HP positivity was defined as any two of the three tests being positive, excluding UBT, and the sensitivity and specificity of any single test alone were determined using this gold standard. Whenever only one test was positive, it was considered to be a false-positive one. Results: With the gold standard used in this study, 59 (66%) patients were diagnosed HP positive. The Heliprobe method detected HP infection with 96.6% sensitivity and 100% specificity and had the best diagnostic performance when compared with all the other methods. The sensitivity and specificity of the other methods for the detection of HP positivity were 89.8% and 100% for RUT, 93.2% and 63.3% for PCR, and 93.2% and 76.6% for HP-HE, respectively. Areas under the receiver-operating characteristic were 0.977 for UBT, 0.947 for RUT, 0.84 for HP-HE, and 0.775 for PCR. Conclusions: Using a combination of invasive diagnostic tests as the gold standard, Heliprobe UBT was found to be highly sensitive and specific for the diagnosis of HP infection in patients with dyspeptic complaints. [ABSTRACT FROM AUTHOR]

The relationship between inflammatory bowel disease and microorganisms was evaluated. The presence of Candida albicans-specific IgM and IgG antibodies in serum samples and the presence of C. albicans in stool and colonal mucosa samples of the patients did not exhibit any significant difference between 21 patients in active stage and 15 patients in remission of ulcerative colitis (UC) (compared with 19 control patients). The invasion of yeast cells to the colonal mucosa was demonstrated by detecting C. albicans DNA using specific PCon1, PCon2, and PspA2 primers in PCR assay. Eighteen of 36 patients (50 %) were found to be DNA positive while in 19 controls only 4 (21 %) were found to be positive. The presence of DNA in the association of the positive serological reactivity is suggested as an important diagnostic marker of UC. [ABSTRACT FROM AUTHOR]

Background and Aim: This study aims to investigate the effects of chronic coffee consumption (>5 years) and type of coffee in non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFLD) and patients who have regular alcohol consumption., Materials and Methods: In this study, 158 healthy individuals and 101 patients with histologically proven NASH were enrolled. The daily amount of coffee intake, amount of alcohol use and type of coffee were calculated for all patients. The degree of steatosis and fibrosis was analyzed by transient elastography and liver ultrasound in non-NASH and by liver biopsy in NASH patients., Results: Patients with a history of coffee consumption (n=132) had lower liver enzyme levels compared to the non-coffee group (n=127) (p=0.001). Serum ALT level was significantly lower [ALT: 21.2±11.7 U/L vs. 56.4±15.6 U/L (p=0.004)], and the liver histopathology was significantly better for patients with a coffee consumption of daily for >5years (p=0.045 for fibrosis score for NASH, p=0.036 for LSM and p=0.015 for CAP measurements for the non-NASH patient)., Conclusion: Coffee seems to have a positive protective effect on liver histology and liver enzyme levels in healthy individuals, in patients with chronic alcohol consumption, NAFLD and NASH. These results are more prominent in patients who drink coffee on a regular daily base for more than five years., Competing Interests: The authors does mot have any conflict of interest., (© Copyright 2020 by Hepatology Forum.)

Background and Aim: Recent studies have reported that the widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN<40U/L) is high for the healthy population. We aimed to find the correct ULN level for men and women in a presumed healthy liver population group., Materials and Methods: The data of 7410 healthy subjects visiting the check-up clinics were retrospectively analysed in this study. Patients were divided in to "healthy liver group" (n=2694) and "high-risk liver group" (n=4716) based on fatty liver on ultrasound, existing of chronic liver disease, ongoing significant alcohol consumption, diabetes mellitus and dyslipidaemia. Receiver operating characteristic (ROC) curves were generated and the area under the curve (AUC) was calculated at the 95 th percentiles for both men and women., Results: The AUC score of ALT for men was 0.92, and the ULN for the serum ALT in men was found as 32.10 U/L (sensitivity of 0.89, specificity 0.85). The AUC score of ALT for women was 0.90, and the ULN for serum ALT was found as 23.15 U/L (sensitivity of 0.90, the specificity of 0.88)., Conclusion: ULN for serum ALT level should be lowered and different cut-off values should be used for men (32.10 U/L) and women (23.15 U/L)., Competing Interests: The authors does mot have any conflict of interest., (© Copyright 2020 by Hepatology Forum.)

Background: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is an indication for orthotopic liver transplantation (OLT) in patients with tumor stage within the United Network for Organ Sharing criteria. The number of patients listed for HBV-related HCC is increasing, while the number of patients listed for HBV-related cirrhosis is declining presumptively because of the availability of more effective oral nucleos(t)ide analogues. This study presents the final, long-term outcome of patients transplanted for HBV-related HCC in the National Institutes of Health (NIH) HBV OLT Study Group., Results: Ninety-eight patients (52.4%) in the NIH HBV OLT cohort underwent OLT for HBV-related HCC. With a mean follow-up of 36.5 months post-OLT, 12 (12.2%) patients developed recurrence of HCC. Multivariate analysis did not find a statistically significant role of gender, tumor stage at OLT, pre-OLT HCC treatment, recurrence of HBV, or duration of HCC diagnosis pre-OLT in predicting HCC recurrence. Serum alpha-fetoprotein (AFP) level >200 ng/mL at transplant was found to be statistically significant in predicting HCC recurrence (p=0.003). HCC recurrence was significantly associated with decreased post-OLT survival., Conclusion: HCC is the most common indication for OLT in patients with chronic hepatitis B in the era of more effective oral antivirals. Serum AFP at the time of OLT is significantly associated with HCC recurrence., (© 2010 John Wiley & Sons A/S.)

Several previous studies found that Asians transplanted for hepatitis B virus (HBV) infection had worse post-transplant outcomes than Caucasians. Data on post-transplant outcomes of African Americans and waitlist outcomes of Asian Americans and African Americans with hepatitis B are scant. The aim of this study was to compare waitlist and post-transplant outcomes among Asian Americans, African Americans, and Caucasians who had HBV-related liver disease. Data from a retrospective-prospective study on liver transplantation for HBV infection were analyzed. A total of 274 patients (116 Caucasians, 135 Asians, and 23 African Americans) from 15 centers in the United States were enrolled. African Americans were younger and more Asian Americans had hepatocellular carcinoma (HCC) at the time of liver transplant listing. The probability of undergoing transplantation and the probability of survival on the waitlist were comparable in the 3 racial groups. Of the 170 patients transplanted, 19 died during a median follow-up of 31 months. The probability of post-transplant survival at 5 years was 94% for African Americans, 85% for Asian Americans, and 89% for Caucasians (P = 0.93). HCC recurrence was the only predictor of post-transplant survival, and recurrence rates were similar in the 3 racial groups. Caucasians had a higher rate of HBV recurrence: 4-year recurrence was 19% versus 7% and 6% for Asian Americans and African Americans, respectively (P = 0.043). In conclusion, we found similar waitlist and post-transplant outcomes among Caucasians, Asian Americans, and African Americans with hepatitis B. Our finding of a higher rate of HBV recurrence among Caucasians needs to be validated in other studies., ((c) 2009 AASLD.)

Increased treatment options that are more efficacious and safe and new knowledge on the natural history of chronic hepatitis B virus (HBV) infection have expanded the indications for therapy in hepatitis B. The question is no longer "Who should be treated?" but "When should treatment be initiated?" Treatment is clearly indicated in patients with life-threatening liver disease (acute liver failure, decompensated cirrhosis, or severe hepatitis flare) and in those with compensated cirrhosis and high levels of serum HBV DNA. For patients with precirrhotic liver disease, treatment indications should be based on clinical, biochemical, or histological evidence of liver disease, such as elevated alanine aminotransferase (ALT) levels, abnormal histology, and high levels of serum HBV DNA. The cutoff for ALT and HBV DNA values are constantly being revised and should be set at a lower level for older patients who may have been infected for a longer period of time. High serum HBV DNA levels persisting for a few decades are associated with increased risk of clinical outcomes, but there is insufficient data to support the initiation of treatment based on high serum HBV DNA alone, particularly in young patients, those with persistently normal ALT levels, and those with a single high HBV DNA level. The decision to initiate treatment at the time of assessment or to defer treatment should take into consideration other factors such as desire to start a family, occupational requirement, family history of hepatocellular carcinoma, access to care and insurance coverage, and commitment to long-term treatment and medication compliance. All patients who are not initiated on treatment should continue to be monitored so treatment can be started if and when the indication arises.

Inflammatory bowel diseases are associated with increased risk for thrombotic complications, In patients with ulcerative colitis (UC) cerebral sinus venous thrombosis (CSVT) is an extremely rare complication. We report a patient with active UC and CSVT. The patient was heterozygous for Factor V Leiden and G20210A prothrombin gene mutations without other identifiable precipitating factors. This patient highlights the need for investigating the patients with UC with thrombotic complications for other thrombophilic states.

The outcome of liver transplantation for hepatitis B has markedly improved in the last two decades. This commentary discusses the findings and limitations of a study by Hwang et al., which retrospectively examined the outcome of 639 adult patients who underwent living donor liver transplantation for hepatitis B. The authors reported a 5-year HBV recurrence rate of 7.3% and concluded that high-dose hepatitis B immunoglobulin (HBIG) monotherapy and rescue antiviral therapy is an effective way to prevent HBV recurrence after liver transplantation. With the availability of safe and effective antiviral agents associated with low rates of drug resistance, HBIG monotherapy is rarely used. The standard approach involves administration of antiviral therapy to suppress HBV replication before transplantation, followed by a combination of HBIG and antiviral therapy after transplantation. Combination prophylaxis permits the dose of HBIG to be reduced, which results in cost savings and reduces rates of HBV recurrence.

Background/aims: Early detection of antiviral drug-resistant mutations enables prompt initiation of rescue therapy. The aim of this study was to determine the accuracy and sensitivity of a new line probe assay in the detection of antiviral drug-resistant HBV mutations., Methods: One-hundred samples from 54 patients with virologic breakthrough during entecavir, lamivudine or adefovir treatment and 21 samples from 21 nucleoside-naïve patients were tested by direct sequencing and an updated line probe assay (Innogenetics, HBV DR v.3) which incorporates probes that can detect mutations at 11 positions of the reverse transcriptase region of the HBV polymerase gene., Results: Complete concordance between line probe and sequencing results was observed for 90/121 samples (74.3%) and 1291/1331 amino acid positions (96.9%). Testing of follow-up samples and clonal analysis of discordant samples confirmed the presence of mutations where line probe assay but not direct sequencing detected mutations. HBV DR v.3 assay consistently detected mutations present in > or = 5% of the virus population when HBV DNA concentration was > or = 4 log10copies/mL., Conclusions: The updated version of the line probe assay (HBV DR v.3) has high concordance with direct sequencing in detecting antiviral drug-resistant mutations but its sensitivity in detecting mutations at some positions needs to be improved.

Emerging data suggest that the hepatitis B virus (HBV) genotype and the precore and core promoter variants impact the outcome of orthotopic liver transplantation (OLT) for hepatitis B. The aim of this study was to determine if there is a correlation between HBV genotype, precore and core promoter variants, and pre- and post-OLT outcomes. Serum samples from patients participating in the National Institutes of Health HBV-OLT study were tested for HBV genotype and precore and core promoter variants. A total of 123 patients were studied: 43% were Asians, 46% were Caucasians, and 8% were African Americans. HBV genotypes A (35%) and C (35%) were the most prevalent, followed by genotypes D and B. Precore and core promoter variants were detectable in 44% and 90% of patients. Patients with genotype C were more likely to have hepatocellular carcinoma (HCC) at listing (P < 0.001). Waitlist mortality was highest among patients with genotype D, while posttransplant mortality was highest among patients with genotype C. Precore or core promoter variants did not correlate with pre- or post-OLT survival. In conclusion, in this US patient population, patients with genotype C were more likely to have HCC at the time of transplant listing and to die after transplant than patients with non-C genotypes. Patients with genotype D had the highest posttransplant survival, but this was offset by higher waitlist mortality. Our study suggests that HBV genotypes but not precore or core promoter variants may have an impact on pre- and post-OLT outcomes of hepatitis B patients., ((c) 2008 AASLD.)

Aim: Neopterin is a marker of cell-mediated immunity. It also has a fundamental role in host-defense reactions, including interactions with reactive oxygen intermediates and the promotion of local and systemic oxidative stress. The present study aimed to assess the importance of serum neopterin levels in patients with non-alcoholic steatohepatitis (NASH)., Methods: Thirty-nine patients with NASH diagnosed by liver biopsy and 32 healthy adults (controls) were enrolled in the study. Serum neopterin levels were measured with an enzyme-linked immunosorbent assay in addition to other biochemical parameters, including liver enzymes. Histopathological examinations were graded as suggested by both the necroinflammatory activity grading system and the NASH scoring system., Results: The mean serum neopterin levels were higher in patients with NASH compared to the controls (24.1 +/- 16.4 vs 16.2 +/- 9.5, P = 0.019). The histological examination of liver biopsies revealed that 34 of the patients with NASH had grade 1 steatohepatitis and only five patients had grade 2 steatohepatitis. A higher serum mean neopterin level was detected in grade 2 patients compared to grade 1 (40.6 +/- 5.6 vs 21.7 +/- 16.1, P = 0.014). A gradual increase was also observed in serum neopterin levels with the increase of the NASH score., Conclusion: The serum neopterin levels were significantly higher in patients with NASH compared to the controls, and levels showed an association with the severity of liver damage.

Ghrelin possesses various biological activities -- it stimulates growth hormone (GH) release, plays a major role in energy metabolism, and is one of the hormones that affects body composition. It also plays a role in modulating immune response and inflammatory processes. In this study we aimed to determine whether serum ghrelin levels had correlation with markers associated with disease activation. We also investigated any probable relationship between serum ghrelin level and nutritional status. Serum levels of ghrelin and its relationship with disease activity and nutritional status were evaluated in 34 patients with ulcerative colitis (UC), 25 patients with Crohn's disease (CD), and 30 healthy controls. Serum ghrelin levels, serum IGF-1 and GH levels, and markers of disease activity (sedimentation, C-reactive protein, and fibrinogen) were measured in all subjects. Body composition and nutritional status was assessed by both direct (by anthropometry) and indirect (by bioimpedance) methods. Serum ghrelin levels were significantly higher in patients with active UC and CD than in those in remission (108 +/- 11 pg/ml vs. 71 +/- 13 pg/ml for UC patients, P < 0.001; 110 +/- 10 pg/ml vs. 75 +/- 15 pg/ml for CD patients, P < 0.001). Circulating ghrelin levels in UC and CD patients were positively correlated with sedimentation, fibrinogen and CRP and was negatively correlated with IGF-1, BMI, TSFT, MAC, fat mass (%), and fat free mass (%). This study demonstrates that patients with active IBD have higher serum ghrelin levels than patients in remission and high levels of circulating ghrelin correlate with the severity of disease and the activity markers. Ghrelin levels in inflammatory bowel disease (IBD) patients show an appositive correlation with IGF-1 and bioelectrical impedance analysis, body composition, and anthropometric assessments. Finally, we arrived at the conclusion that ghrelin level may be important in determination of the activity in IBD patients and evaluation of nutritional status.

Background/aims: We sought to identify mutations associated with treatment failure to adefovir (ADV) and to determine virologic response to tenofovir (TDF) alone and in combination with emtricitabine (FTC) in these patients., Methods: Serum samples prior to and after the change in treatment to TDF/TDF+FTC from 13 patients were analyzed by direct sequencing and clonal analysis., Results: ADV-resistant mutations, rtA181V and rtN236T, were detected on direct sequencing in 3 of 8 patients who had virologic breakthrough. Among patients with suboptimal virologic response, rtA181T, rtI233V, and rtN236T were present on clonal analysis in 3 patients. Ten patients received TDF, 8 achieved virologic response. One had ADV-resistance at baseline and persistence of ADV-resistant mutations during TDF treatment, addition of FTC resulted in a further decrease in HBV DNA. Another patient had no ADV-resistance at baseline, and selection of ADV-resistant mutations during TDF treatment. All 3 patients who received TDF+FTC had undetectable HBV DNA within 3-12 months including 2 who had ADV-resistance at baseline., Conclusions: TDF monotherapy is effective for patients with virologic breakthrough or suboptimal response to ADV, but combination therapy with a nucleoside analogue should be considered in patients with ADV-resistance. No novel mutations were detected.

Endothelin-1 (ET-1) is known to play an important role in hepatic fibrosis. ET-1 is also a mediator that is elevated in conditions such as insulin resistance, hyperglycemia, oxidative stress, and endothelial cell dysfunction. In this study, we investigated whether ET-1 has a role in determining the severity of liver fibrosis in NASH. Also, the relation between ALT levels, obesity, diabetes, and AST/ALT ratio and fibrosis and ET-1 level was sought. A total of 92 patients were enrolled in the study. The patients were categorized into three groups: group 1, patients with elevated transaminase levels who were diagnosed as NASH by liver biopsy (n=40); group II, patients with only hepatosteatosis determined by biopsy but having elevated transaminase levels (n=12); and group III, patients with hepatosteatosis observed by ultrasonography, having normal transaminase levels (n=40). The serum ET-1 level was measured by an appropriate ELISA kit for all patients. Mean serum ET-1 level was statistically significantly higher in the NASH group compared to the other two groups (15.56+/-4.63 vs 6.75+/-2.46 and 5.74+/-2.34 micromol/L; P < 0.01). Mean serum ET-1 levels in NASH patients with grade I, grade II, and grade IV fibrosis were 14.06+/-0.92, 17.70+/-2.32, and 20.40+/-1.40 micromol/L, respectively. None of the patients were identified as grade III fibrosis. It was found that the serum ET-1 level showed a statistically significant increase as fibrosis severity increased in NASH patients (P < 0.05). In conclusion, the serum ET-1 level is higher in NASH patients compared to patients having only steatosis. There appears to be a correlation between severity of fibrosis and serum ET-1 level in NASH patients. It has been found that NASH patients having a twofold increase in their ALT levels had higher ET-1 levels and a more severe grade of fibrosis.

Aim: To investigate the prevalence of celiac disease serologic markers (antigliadin IgA, IgG, and anti-endomysial IgA) in patients with reflux esophagitis and to detect the relationship between reflux esophagitis and celiac disease (CD)., Methods: This study was performed prospectively between January 2003 and January 2004. Sixty-eight adult reflux esophagitis patients and 40 people as control group for symptoms related with gastrointestinal system were enrolled in this study. The diagnostic work-up included an accurate medical history with gastrointestinal symptoms, routine laboratory measurements, the detection of antibodies against gliadin (IgA and IgG) and endomysium (IgA), and an upper endoscopy with postbulbar biopsy., Results: IgA-AGA and IgG-AGA were positive at 8.8% and 10.3% in patients with reflux esophagitis. In control group, it was found that 10% people had positive IgA-AGA, and 7.5% people had positive IgG-AGA. There was no significant relationship between patients and control group regarding positive IgA-AGA and IgG-AGA. The patients and persons in control group had no positive IgA-EMA. On postbulbar biopsies, no finding was detected concerning celiac disease. There were no symptoms and signs for gluten enteropathy in patients and control group., Conclusion: This review supports that an association does not exist between celiac disease and reflux esophagitis. We think these diseases exist independently from each other.

Background: Isolated thrombocytopenia is a common manifestation of hepatitis C virus (HCV) infection. There is no established treatment modality for this condition. The efficacy of standard interferon (IFN) monotherapy has been reported in some studies. The major disadvantage of this treatment is the high rate of recurrence due to viral breakthrough during the first 12 weeks of treatment. Pegylated IFNs are now the standard regimen for chronic hepatic disease due to HCV infection. However, due to a lack of evidence, pegylated IFNs are not widely used for HCV-related isolated thrombocytopenia., Objective: The aim of this report was to present the case of a male patientwith severe symptomatic thrombocytopenia due to HCV infection., Methods: Thrombocytopenia was treated with pegylated IFN plus ribavirin., Results: Although standard IFN monotherapy failed to achieve virologic and hematologic improvement, therapy with pegylated IFN alfa-2a plus ribavirin was associated with both virologic and hematologic improvement without any significant adverse effects., Conclusions: Pegylated IFN plus ribavirin was effective in this patient for thetreatment of HCV-related thrombocytopenia. However, further research is needed to define the response rate in different patient populations.