SUMMARY Chronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA-sequencing in primary human hepatocytes activated with synthetic dsRNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.13, we discovered a novel, transiently induced region that harbors dinucleotide variant ss469415590 (TT/ΔG), which is in high linkage disequilibrium with rs12979860, a genetic marker strongly associated with HCV clearance. ss469415590-ΔG is a frame-shift variant that creates a novel primate-specific gene, designated interferon lambda 4 (IFNL4), which encodes a protein of moderate similarity with IFNL3. Compared to rs12979860, ss469415590 is more strongly associated with HCV clearance in individuals of African ancestry, whereas it provides comparable information in Europeans and Asians. Transient over-expression of IFNL4 in a hepatoma cell line induced STAT1/STAT2 phosphorylation and expression of interferon-stimulated genes. Our findings provide new insights into the genetic regulation of HCV clearance and its clinical management.

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AA with chronic hepatitis C genotype 1 have lower rates of virologic response to peginterferon and ribavirin than CA. These differences are not explained by disease characteristics, baseline viral levels, or amount of medication taken.

Analyses of deltaic facies successions highlight recurring ichnological patterns that reflect a variety of physicochemical stresses imposed upon infaunal organisms by the interaction of various delta-front processes. Analysis of numerous ancient deltaic deposits in Canada, the United States, Australia, and offshore Norway persistently show reductions in bioturbation intensity and impoverishment in ichnological diversity, compared to those of nondeltaic shorelines. Some facies locally demonstrate sporadic colonization and recolonization of substrates left denuded by episodic depositional conditions. Deltaic ichnological suites also locally display size reductions of ichnogenera and a paucity of suspension-feeding ethologies. Resulting trace-fossil suites are overwhelmingly dominated by depositfeeding behaviors, even in sandy facies. Such ichnological characteristics largely reflect increased sedimentation rates and heightened fluvial discharge, which serve to impede infaunal colonization. River-derived stresses are profound: salinity changes, hypopycnal-flow-induced water turbidity, distributary flood discharges with accompanying phytodetrital (comminuted plant debris) pulses, hyperpycnal-flow-induced sediment gravity flows, and fluid-mud deposition all conspire to produce the overall depauperate nature of the ichnological assemblage. Freshet-discharge events during river floods, accompanied by hyperpycnal conditions, may lead to the episodic introduction of reduced-salinity waters immediately above the sediment-water interface in delta-front and prodelta depositional settings. Such conditions may facilitate development of synaeresis cracks and promote reductions in infaunal populations. Wave energy generally buffers fluvial effects, by dispersing suspended sediment offshore and encouraging the thorough mixing of waters of contrasting salinity. High mud concentrations near the delta front damp wave energy, however, limiting its effectiveness in remediating the benthic ecosystem, particularly immediately following distributary flood discharges and storm events. In wavedominated settings, strong alongshore drift also operates to extend river-derived stresses considerable distances downdrift from distributary mouths. Where asymmetric deltas are formed, markedly different ichnological expressions are expressed on either side of distributary-channel mouths. Updrift settings typically retain classic shoreface assemblages, whereas downdrift environments commonly acquire markedly stressed suites. Storm energy may be effective in dispersing mud and mixing waters, but it also results in erosion and episodic sediment deposition. Concomitant precipitation induces river floods, returning river-derived stresses to the delta front. Tidal energy and its effects on the infaunal communities of deltas are poorly documented. Tidal flux may trap mud plumes against the delta front, elevating water turbidity. Pronounced mud flocculation coupled with increased settling velocity associated with tidal mixing also leads to rapid deposition ...

Terlipressin plus albumin was associated with greater improvement in renal function vs albumin alone in patients with cirrhosis and HRS-1. Patients had similar rates of HRS reversal with terlipressin as they did with albumin. ClinicalTrials.gov no: NCT01143246.