Complete Recovery After Immunosuppressive Treatment Change in a Patient With Posttransplant Lymphoproliferative Disorder.

Posttransplant lymphoproliferative diseases are a rare but important cause of morbidity and mortality secondary to immunosuppression after solid-organ or bone marrow transplant. Generally, posttransplant lymphoproliferative diseases develop in the first 2 years after transplant, when immunosuppressive therapy is the most intense. Change or reduction in immunosup - pressive treatment is an option for treatment of posttransplant lymphoproliferative diseases. We evaluated the treatment of a patient with posttransplant lymphoproliferative disease after liver transplant. A 64-year-old man underwent liver transplant from a living donor (the patient's son) in 2011 to treat hepatocellular cancer secondary to chronic hepatitis B. Tacrolimus and mycophenolate mofetil were used for immunosuppression through 9 years after liver transplant. In the abdominal computed tomography performed in response to abdominal pain during follow-up in March 2019, multiple solid lesions were observed. A liver biopsy revealed posttransplant lymphoproliferative disease with diffuse large B-cell lymphoma. Fluorine-18 positron emission tomography/computed tomography imaging of the patient showed no pathology in favor of primary lymphoproliferative disease. Mycophenolate mofetil and tacrolimus treatment was changed to everolimus. In the follow-up dynamic magnetic resonance imaging examination that was performed at 3 months after treatment change, we observed that the lesion at liver segment 6 had regressed to 30 mm and several lesions with similar features were observed in the right lobe of the liver. Additional liver biopsy results were compatible with complete remission. The patient's clinical symptoms had fully regressed at 18 months after the diagnosis of PTLD, at the time of this writing. Ongoing radiological and clinical follow-up has shown complete remission. Change from calcineurin treatment to treatment with an inhibitor of the mechanistic target of rapamycin may be an essential and new option for treatment of posttransplant lymphoproliferative disease after liver transplant.

Metabolomics and microbial composition increase insight into the impact of dietary differences in cirrhosis.

BACKGROUND & AIMS: Dietary changes can modulate gut microbiota and interact with cirrhosis. Our prior study demonstrated that microbial diversity was higher in cirrhotics from Turkish vs the USA, which was associated with lower risk of 90-day hospitalizations. We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets. METHODS: In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied. Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet. Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries. Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated. RESULTS: Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA. Plasma metabolomics demonstrated higher relative lactate levels in Turkey vs the USA. The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and the USA, with reduced lipids and phosphocholines. Phosphocholines were significantly lower in patients hospitalized in 90 days (P = .03). Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients. CONCLUSIONS: A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis. These altered diet-microbial interactions could potentially affect the 90-day hospitalization risk.

Effectiveness of fixed-dose combination of paritaprevir, ritonavir, ombitasvir, and dasabuvir in patients with chronic hepatitis C virus infection and chronic kidney diseases: real-life experiences.

INTRODUCTION: Both hepatitis C virus infection (HCV) and chronic kidney disease (CKD) have been comorbid illnesses with increasing morbidity and mortality. The present study was conducted to present real-life experiences about treatment of HCV and CKD with a fixed-dose combination of paritaprevir 150 mg/day, ritonavir 100 mg/day as a booster, ombitasvir 25 mg/day, and dasabuvir 250 mg twice/day, the PROD regimen. PATIENTS AND METHODS: This was a multicenter, retrospective cohort study. Seventy-five patients with both HCV and CKD were treated with a PROD-based regimen with or without ribavirin. Fifty-three of 75 patients were on maintenance hemodialysis program. Seven patients had compensated liver cirrhosis. The patients with genotype 1a or compensated liver cirrhosis were treated with the PROD regimen and ribavirin in a dose of 200 mg every other day for 12 weeks. The patients with genotype 1b were treated with PROD for 12 weeks. The patients with genotype 4 were treated with a combination of paritaprevir, ritonavir, ombitasvir, and ribavirin 200 mg every other day. RESULTS: All patients except one were HCV-RNA negative (98.6%) at the end of treatment. One patient had decompensated after the fourth day of therapy. She stopped the treatment, and she was exitus after 2 months. Two patients died of reasons not related to the drugs 2 months after negativity of HCV-RNA. Sustained viral rate 12 weeks after treatment was found in 96% of the patients. CONCLUSION: The PROD regimen was very effective and safe for treatment in patients with HCV and CKD who were in stages 4 and 5.

Diet affects gut microbiota and modulates hospitalization risk differentially in an international cirrhosis cohort.

The relative ranking of cirrhosis-related deaths differs between high-/middle-income countries. Gut microbiome is affected in cirrhosis and is related to diet. Our aim was to determine the effect of differing dietary habits on gut microbiota and clinical outcomes. Outpatient compensated/decompensated patients with cirrhosis and controls from Turkey and the United States underwent dietary and stool microbiota analysis. Patients with cirrhosis were followed till 90-day hospitalizations. Shannon diversity and multivariable determinants (Cox and binary logistic) of microbial diversity and hospitalizations were studied within/between groups. Two hundred ninety-six subjects (157 U.S.: 48 controls, 59 compensated, 50 decompensated; 139 Turkey: 46 controls, 50 compensated, 43 decompensated) were included. Patients with cirrhosis between cohorts had similar Model for End-Stage Liver Disease (MELD) scores. American patients with cirrhosis had more men, greater rifaximin/lactulose use, and higher hepatitis C/alcohol etiologies. Coffee intake was higher in Americans whereas tea, fermented milk, and chocolate intake were higher in Turkey. The entire Turkish cohort had a significantly higher microbial diversity than Americans, which did not change between their controls and patients with cirrhosis. In contrast, microbial diversity changed in the U.S.-based cohort and was the lowest in decompensated patients. Coffee, tea, vegetable, chocolate, and fermented milk intake predicted a higher diversity whereas MELD score, lactulose use, and carbonated beverage use predicted a lower microbial diversity. The Turkish cohort had a lower risk of 90-day hospitalizations. On Cox and binary logistic regression, microbial diversity was protective against 90-day hospitalizations, along with coffee/tea, vegetable, and cereal intake. CONCLUSION: In this study of patients with cirrhosis and healthy controls from the United States and Turkey, a diet rich in fermented milk, vegetables, cereals, coffee, and tea is associated with a higher microbial diversity. Microbial diversity was associated with an independently lower risk of 90-day hospitalizations. (Hepatology 2018;68:234-247).