Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.

Adult Living Donor Liver Re-Transplant Following Late Pediatric Liver Transplant Failure: A Case Report.

BACKGROUND Re-transplant of a late failing living donor liver graft using another graft from another living donor is a rare occurrence and is associated with high mortality due to the complexity of the procedure. There are only a few such case series reported in the literature, mainly from South Asia and Japan, where living donor liver transplant is commonly performed, and there are no such reports from Western countries. CASE REPORT This is a case of living donor liver re-transplant for a 28-year-old recipient whose graft failed 14 years after his primary living donor transplant for primary sclerosing cholangitis. The second transplant was a right-lobe graft obtained from a living donor. The presence of portal vein thrombosis in the setting of high Model for End-Stage Liver Disease (MELD) score added to the complexity of the case. The procedure was concluded successfully with an uneventful post-operative course. The patient was discharged 3 weeks after the procedure. One-year follow-up showed a normally functioning graft. CONCLUSIONS Successfully re-transplanting a patient with a failing living donor liver graft from a living donor is possible if sufficient surgical expertise is available and the risk and benefit are carefully considered. This is especially important in countries where a cadaveric graft is difficult to obtain due to organ scarcity.

Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation.

Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA), myeloperoxidase activity (MPO), expression of nuclear factor kappa B (NF-κB) p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion (P < 0.001) and acidity (P < 0.0001) and gastric ulcer index scores (P < 0.001). and augmented the gastric mucosal defense. Vanillin significantly restored the depleted gastric wall mucus levels (P < 0.0001) induced by ethanol and also significantly attenuated ethanol induced inflammation and oxidative stress by the suppression of gastric MPO activity (P < 0.001), reducing the expression of NF-κB p65 and the increased MDA levels (P < 0.001). Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol. Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture.

Liver transplantation for hepatitis B virus: Decreasing indication and changing trends.

AIM: To evaluate the indication and outcome of hepatitis B virus (HBV)-related liver transplantation (LT) in the era of newer antiviral agents. METHODS: We collected data on all patients who underwent transplantation at King Faisal Specialist Hospital and Research Center. These data included demographic, perioperative and long-term postoperative follow-up data including viral serological markers, HBV DNA, and repeated liver imaging. Between January 1990 and January 2012, 133 patients (106 males and 27 females) underwent LT for HBV-related cirrhosis at our center. All patients were followed up frequently during the first year following transplantation, according to our standard protocol; follow-up visits occurred every 3-6 mo thereafter. Breakthrough infection was defined as re-emergence of HBV-DNA or hepatitis B surface antigen (HBsAg) while on treatment. Five patients transplanted prior to 1992 did not receive immediate posttransplant anti-HBV prophylaxis; all other patients were treated with HBIG and at least one nucleos(t)ide analog. RESULTS: One hundred and thirty-three patients underwent LT for HBV and were followed for a median of 82 mo (range: 1-274). The rates of post-LT survival and HBV recurrence during the follow-up period were 89% and 11%, respectively. The following factors were associated with disease recurrence: younger age (44.3 ± 16.2 years vs 51.4 ± 9.9 years, P = 0.02), positive pretransplant hepatitis B e antigen (HBeAg) (60% vs 14%, P < 0.0001), detectable pretransplant HBV DNA (60% vs 27%, P = 0.03), positive posttransplant HBsAg (80% vs 4%, P < 0.0001) and positive posttransplant HBeAg (27% vs 1%, P < 0.0001). Forty-four (33%) patients had hepatocellular carcinoma (HCC). In the first (pre-2007) group, HBV was the second leading indication for LT after hepatitis C virus infection. A total of 64 transplants were performed, including 46 (72%) for decompensated HBV cirrhosis, 12 (19%) for decompensated cirrhosis complicated by HCC and 6 (10%) for compensated cirrhosis complicated by HCC. In the second group, nonalcoholic steatohepatitis surpassed HBV as the second leading indication for LT. A total of 69 HBV related transplants were performed, including 43 (62%) for decompensated HBV cirrhosis, 7 (10%) for decompensated cirrhosis complicated by HCC and 19 (27.5%) for compensated cirrhosis complicated by HCC. There was a significant (P = 0.007) increase in the number of transplants for compensated cirrhosis complicated by HCC. CONCLUSION: The use of potent anti-HBV agents has led to a changing trend in the indications for LT. HBV is currently the third leading indication for LT in this hyperendemic area.

Revising the upper limit of normal for levels of serum alanine aminotransferase in a Middle Eastern population with normal liver histology.

BACKGROUND: Recently, the upper limits of normal (ULN) for alanine-aminotransferase (ALT) has been recommended to be lowered to ≤ 30 U/l in men and ≤ 19 U/l in women. AIM: To evaluate the ALT concentrations in a healthy Middle Eastern population with biopsy-proven normal liver tissue. METHODS: ALT values were calculated from 175 consecutive Saudi potential living liver donors who underwent a liver biopsy as part of a stepwise pretransplant workup. RESULTS: The mean age of the 110 potential donors with normal liver histology was 27 ± 6.2 years for men and 38.6 ± 7.1 years for women. The mean body mass index (BMI) levels were 23.0 ± 3.5 kg/m(2) for men and 24.7 ± 3.25 kg/m(2) for women, and the ALT levels were higher in male patients (22.6 ± 9 vs. 16.4 U/l ± 8, p value = 0.003). Multivariate linear regression showed that BMI and sex were independent variables that were positively associated with the levels of ALT (p < 0.0001). Moreover, when we analyzed donors according to the Prati criteria, 63 (36.0 %) of the individuals were classified into this subgroup. The mean ALT concentration was 12.9 U/l ± 4.5 in women and 19.7 U/l ± 6.9 in men, and these values were significantly lower than those obtained from subjects who did not fit the Prati criteria (19.4 U/l ± 1.8, p = 0.04 for women and 29.0 U/l ± 12.1, p = <0.0001 for men). Thus, we calculated healthy ALT values of 33 IU/l for men and 22 IU/l for women. CONCLUSIONS: The ULN for ALT levels in Middle Eastern populations should be lowered, including separate values for males and females. Furthermore, metabolic parameters were shown to have a significant effect on ALT levels.

Treatment of genotype 4 hepatitis C recurring after liver transplantation using a combination of pegylated interferon alfa-2a and ribavirin.

BACKGROUND: Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and tends to be more aggressive. Data on post-transplant HCV genotype 4 treatment is scarce. The aim of this study is to assess the safety and efficacy of pegylated interferon alpha-2a (PEG-IFN) in combination with ribavirin in the treatment of recurrent HCV genotype 4 after LT. METHODS: Twenty-five patients infected with HCV genotype 4 were treated with PEG-IFN alpha-2a at a dose of 180 µg/week in addition to 800 mg/day of ribavirin (the dose was adjusted within the tolerated range of 400-1,200 mg). Pretreatment liver biopsies were obtained from all patients. Biochemical and virological markers were assessed before, during, and after treatment. RESULTS: Twenty-two patients (88%) achieved an early virological response (EVR) (12 patients tested negative for HCV-RNA). Fifteen (60%) and 14 patients (56%) achieved an end of treatment virological response (ETVR) and a sustained virological response (SVR), respectively. Five patients had advanced pretreatment liver fibrosis. Pretreatment ALT was elevated in 24 patients (96%). The most common adverse effects were flu-like symptoms and cytopenia. Eighteen patients (72%) required erythropoietin alpha and/or granulocyte-colony stimulating factor as a supportive measure. One patient developed severe rejection complicated by sepsis, renal failure, and death. Other adverse effects included depression, mild rejection, impotence, itching, and vitiligo. CONCLUSIONS: Post-transplant treatment with pegylated interferon alpha-2a and ribavirin achieved SVR in 56% of liver transplant recipients with chronic HCV genotype 4 infection. The combination was relatively safe and exhibited a low rate of treatment withdrawal.