Background:The liver plays a central role in ingestive behavior; alterations in metabolic signaling to the brain stem as a result of chronic liver disease could influence intake. Objective: We examined the influence of metabolic sequelae of liver disease on nutrient intake and nutritional status. Design: Nutritional status and spontaneous dietary intake were examined in 65 cirrhotic patients and 14 control subjects. The response to feeding was investigated in 14 control subjects and a subgroup of 31 cirrhotic patients. Comparisons were made between patients with primary biliary cirrhosis (PBC) and hepatocellular cirrhosis (HC). Results: Patients were nutritionally depleted. The fasting rate of lipid oxidation in the HC group was greater than in the control group (P < 0.01). In the fasting state, only HC patients were hyperinsulinemic [121.2 ± 78.5 compared with 41.3 ± 18.6 pmol/L in control subjects (P < 0.001) and 64.7 ± 15.8 pmol/L in PBC patients (P < 0.05)] and this persisted during the response to feeding. In the fed state, the magnitude of change in carbohydrate oxidation was greatest in the HC group (HC: 34.6%; control: 23.1%; PBC: 25.2%). Carbohydrate and energy intakes of the HC group were lower than in control subjects (carbohydrate: 193 ± 38.3 compared with 262 ± 48.1 g/d, P < 0.05; energy: 6.29 ± 1.40 compared with 9.0 ± 2.12 MJ/d, P < 0.05). Conclusions: Reductions in carbohydrate intake could be mediated by hyperinsulinemia and compounded by preferential uptake of carbohydrate. This may enhance gastrointestinal satiety signaling and contribute to hypophagia.Am J Clin Nutr 1999;69:331-7.

Objectives: Chronic hepatitis C-infected patients who do not respond to nonstructural 5A inhibitor-containing regimens have few treatment options. It is unclear if patients who fail glecaprevir/pibrentasvir (G/P) (Mavyret) can be re-treated with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) because the latter's registration trials antedated the availability of the former. Methods: Adherent virologic failures to G/P were re-treated with 12 weeks of SOF/VEL/VOX, and all subjects underwent resistance testing at baseline and again with subsequent relapse. Results: Ninety-four percent of subjects achieved sustained virologic response with re-treatment, despite 90% of 31 subjects harboring nonstructural 5A inhibitor resistance-associated mutations at baseline. DISCUSSION: SOF/VEL/VOX is an effective regimen for virologic failures to G/P.

Background & AimsThe host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression.MethodsWe evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing.ResultsResults were as follows: (1) the average diversity among cases with seronegative acute HCV infection was 4.2 times higher than among uninfected controls; (2) the diversity level among cases with chronic HCV infection was 96.1 times higher than among uninfected controls; and (3) the diversity was 23.1 times higher among chronic than acute cases. In 2 patients who were followed up during combined interferon and ribavirin therapy, mtDNA nucleotide diversity decreased dramatically after the completion of therapy in both patients: by 100% in patient A after 54 days and by 70.51% in patient B after 76 days.ConclusionsHCV infection strongly affects mtDNA genetic diversity. A rapid decrease in mtDNA genetic diversity observed after therapy-induced HCV clearance suggests that the effect is reversible, emphasizing dynamic genetic relationships between HCV and mitochondria. The level of mtDNA nucleotide diversity can be used to discriminate recent from past infections, which should facilitate the detection of recent transmission events and thus help identify modes of transmission.

Summary Background In 2017, the hepatitis C treatment regimens sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) and glecaprevir/pibrentasvir (G/P) received approval from the U.S. Food and Drug Administration. Although both SOF/VEL/VOX (NS5B polymerase inhibitor/NS5A inhibitor/NS3/4A protease inhibitor) and G/P (NS3/4A protease inhibitor/NS5A inhibitor) are pangenotypic regimens, they are indicated for distinct subsets of patients with hepatitis C. Aim To compare and contrast available safety and efficacy data for SOF/VEL/VOX and G/P and outline their clinical utility. Methods For each of the regimens, this review outlines the indications, safety information, and the major clinical studies in which SOF/VEL/VOX and G/P were evaluated. Results SOF/VEL/VOX is positioned as a salvage regimen for patients previously treated with NS5A inhibitors and for genotype 1a‐ and 3‐infected patients who had failed other sofosbuvir‐containing regimens. G/P is the first pangenotypic regimen with an 8‐week duration for treatment‐naïve, non‐cirrhotic patients, and it is indicated for patients with any genotype who have advanced kidney disease, including those on dialysis. Conclusion The addition of SOF/VEL/VOX and G/P to existing hepatitis C treatment options will expand the number of patients who are eligible for and responsive to treatment, thus increasing the possibility of eliminating hepatitis C as a public health issue.