Fatih Karakaya

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV‐1 study

In a proof‐of‐concept (POC) study, the oral prenylation inhibitor, lonafarnib (LNF), decreased hepatitis D virus (HDV) RNA during 4 weeks of treatment. Here, we explored optimal LNF regimens. Fifteen patients (five groups; 3 per group) completed dosing as follows: (1) LNF 200 mg twice‐daily (BID; 12 weeks); (2) LNF 300 mg BID (12 weeks); (3) LNF 100 mg thrice‐daily (5 weeks); (4) LNF 100 mg BID + pegylated interferon alfa (PEG‐IFNα) 180 μg once‐weekly (QW; 8 weeks); and (5) LNF 100 mg BID + ritonavir (RTV) 100 mg once‐daily (QD; 8 weeks). Tolerability and efficacy were assessed. Higher LNF monotherapy doses had greater decreases in HDV viral load than achieved in the original POC study. However, this was associated with increased gastrointestinal adverse events. Addition of RTV 100 mg QD to a LNF 100 mg BID regimen yielded better antiviral responses than LNF 300 mg BID monotherapy and with less side effects. A similar improvement was observed with LNF 100 mg BID + PEG‐IFNα 180 μg QW. Two of 6 patients who received 12 weeks of LNF experienced transient posttreatment alanine aminotransferase (ALT) increases resulting in HDV‐RNA negativity and ALT normalization. Conclusion: The cytochrome P450 3A4 inhibitor, RTV, allows a lower LNF dose to be used while achieving higher levels of postabsorption LNF, yielding better antiviral responses and tolerability. In addition, combining LNF with PEG‐IFNα achieved more substantial and rapid HDV‐RNA reduction, compared to historical responses with PEG‐IFNα alone. Twelve weeks of LNF can result in posttreatment HDV‐RNA negativity in some patients, which we speculate results from restoring favorable immune responses. These results support further development of LNF with RTV boosting and exploration of the combination of LNF with PEG‐IFN. (Hepatology 2018;67:1224‐1236)

Factors related to low serum vitamin B12 levels in elderly patients with non‐atrophic gastritis in contrast to patients with normal vitamin B12 levels

Vitamin B12 deficiency is frequent in older patients, and the main reason is pernicious anemia. However, vitamin B12 deficiency can occur in patients who do not have atrophic gastritis. The aim of the present study was to investigate factors affecting serum vitamin B12 levels in older patients with non‐atrophic gastritis.

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).

Discontinuation of lamivudine treatment in HBeAg-negative chronic hepatitis B: a pilot study with long-term follow-up

BACKGROUND Finite treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with nucleoside/nucleotide analogues (NAs) is important in resource-limited countries. Outcome of treatment discontinuation in patients on long-term lamivudine (LVD) was assessed in a single centre observational pilot study in the current study. METHODS Non-cirrhotic patients on LVD for at least 5 years with undetectable HBV DNA on at least two consecutive assessments were offered to stop treatment. Biochemical, serological and virological measures were determined at 3-6 month intervals after treatment discontinuation. Serum quantitative hepatitis B surface antigen (HBsAg) was determined at treatment discontinuation and 5-6 years thereafter. NA treatment was re-instituted in patients with confirmed viral rebound defined as HBV DNA >20,000 IU/ml. Relapser patients were no longer followed but were re-assessed 6 years after treatment cessation. RESULTS LVD was discontinued in 23 patients. 8 patients relapsed within 1 year and NA treatment was restarted; 15 patients (65%) were non-relapsers. Thirteen of them were followed for at least 5 years. Two patients had undetectable HBV DNA throughout the follow-up period. In the rest, HBV DNA fluctuated at low levels. Two patients cleared HBsAg 24 and 36 months after stopping treatment. Quantitative HBsAg levels 5-7 years after treatment discontinuation were lower in non-relapser compared to relapser patients (1.21 IU/ml ±0.98 versus 2.71 ±0.76; P=0.002). Of 8 relapser patients 1 patient had HBsAg levels less than 100 IU/ml compared to 11 out of 13 non-relapser patients (P=0.0022). CONCLUSIONS These data suggest that cessation of NA treatment is a viable option after a reasonable treatment duration in patients with HBeAg-negative CHB and that HBsAg clearance may become an achievable target in these patients.

Interferon Treatment Duration in Patients With Chronic Delta Hepatitis and its Effect on the Natural Course of the Disease

Background Interferon is the only treatment option in chronic delta hepatitis (CDH). A CDH database (333 patients, 161 with interferon treatment history) was analyzed for effects of treatment duration on virologic response and clinical outcomes. Methods Ninety-nine CDH patients who received at least 6 months of interferon were selected. Maintained virologic response (MVR) was defined as hepatitis D virus RNA negative for 2 years after treatment discontinuation. Cumulative median interferon treatment duration was 24 months (range 6-126 months), with a median of 2 courses (range 1-8). Post-treatment median follow-up was 55 months (24-225 months). Results Thirty-five patients achieved MVR. Cumulative probability of MVR increased with treatment duration and reached 50% at 5 years. Patients with MVR were less likely to die from liver disease or develop complications compared to patients without MVR (P = .032, P = .006, respectively). Cirrhosis at baseline and no response to therapy (odds ratio 16.1 and 5.23, respectively) predicted an adverse endpoint. Hepatitis B surface antigen clearance occurred in 37% of patients with MVR. Conclusion Viral response to interferon increases with treatment duration and favorably affects the natural course of disease. Interferon treatment duration has to be individualized with careful post-treatment assessment.

Similarities and differences between older and young adult patients with celiac disease

Celiac disease is an autoimmune enteropathy with variable clinical symptoms. Elderly patients can have different manifestations from those of young patients. The aims of the present study were to investigate whether any differences or similarities exist between older and young patients with celiac disease with a special emphasis on concurrent autoimmune diseases.

Percutaneous treatment with the Örmeci technique for hydatid disease located in the spleen: Single center experience for twenty six years

BACKGROUND/AIMS Hydatid disease remains an important global socioeconomic health problem, particularly in the endemic areas. Although half of the patients show no symptoms, hydatid cysts should be treated because of their fatal complications. The aim of this study is to present the long-term results of percutaneous treatment of hydatid disease using the Örmeci technique. MATERIALS AND METHODS Forty-nine patients with 54 cystic lesions were diagnosed with hydatid disease. Twenty-seven of the 54 hydatid cysts located in the spleen were punctured with a 22-gauge Chiba needle through the parenchyma of the spleen under sonographic guidance as a one-step procedure. For every 1 cm of the long diameter of the cyst lesion, 3 cc of fluid from the cysts was aspirated. For each centimeter of the long diameter, 2 cc of pure alcohol (96%) and 1 cc of polidocanol (1%) were injected into the cysts. Five out of 27 patients did not participate in the follow-up. RESULTS The 22 patients who were treated using the percutaneous Örmeci technique were followed up for a mean±SD (median) of 50.32±65.30 (26.00) months (minimum 4 and maximum 298 months). All patients except one were successfully treated. No deaths or major complications were noted. Seven patients experienced minor complications. CONCLUSION Percutaneous treatment with the Örmeci technique is a safe, effective, cheap, and reliable method that does not interfere with splenic functions, and this outpatient procedure should be the method of choice for a surgery alternative.

Rare But Life-Threatening Complication of Hydatid Disease

Cystic echinococcosis is an infectious disease that is potentially associated with the biliary tract. Of thousand cases of hydatid cysts that were successfully treated by the Örmeci method, only two presented with cholangitis subsequent to the percutaneous treatment. These cases were treated with endoscopic retrograde cholangiopancreatography, and this study provides details regarding the clear fistulization of hydatid cysts into the biliary tract.

Utility of three prognostic risk scores in predicting outcomes in elderly non-malignant patients after percutaneous gastrostomy

Background/ObjectivesPercutaneous endoscopic gastrostomy is a method of providing enteral feeding to patients who cannot take adequate oral nutrition. The aims of this study were to determine the performance of malnutrition and mortality scoring systems for predicting short and long-term mortality in elderly patients who had undergone gastrostomy procedure due to non-malignant conditions. Design: Retrospective cohort study.SettingUniversity hospital in Turkey.Participants155 individuals aged 65 and older principally hospitalized for non-malignant diseases and require percutaneous endoscopic gastrostomy.Measurements“Geriatric Nutritional Risk Index”, “Malnutrition Universal Screening Tool” (MUST) and “Portsmouth- Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity” (P-POSSUM) scores were calculated. The ability of these scores to predict mortality was determined.ResultsThe mean survival period was 9.59±6.0 months and mortality rate was 80.6%. The performance of “Geriatric Nutritional Risk Index” was superior to MUST and P-POSSUM in predicting long-term survival of gastrostomy patients; 94.1% of patients were alive with a cut-off value of 90 for “Geriatric Nutritional Risk Index” (sensitivity: 92% CI 85.9-95.6 and specificity: 90% CI 74.3-96.5). Survival analysis showed that patients (n=7) with a “Geriatric Nutritional Risk Index” score of > 98 before the gastrostomy had the longest survival time, while patients (n=102) with a “Geriatric Nutritional Risk Index” score of < 82 had the worst outcome.ConclusionsA scoring system such as “Geriatric Nutritional Risk Index” should be considered as a risk scoring system for predicting early and late mortality at gastrostomy and also assist in making decisions such as timing of gastrostomy procedure.

Comparison of three scorıng systems for risk stratifıcation in elderly patıents wıth acute upper gastrointestinal bleedıng.

Acute gastrointestinal bleeding is a potentially life‐threatening condition that requires rapid assessment and dynamic management. Several scoring systems are used to predict mortality and rebleeding in such cases. The aim of the present study was to compare three scoring systems for predicting short‐term mortality, rebleeding, duration of hospitalization and the need for blood transfusion in elderly patients with upper gastrointestinal bleeding.