Despite the growing availability of noninvasive and faster diagnostic modalities, biopsy remains an important tool in the diagnosis and management of liver diseases. However, it is not uncommon that liver biopsies reveal normal or near normal histologic findings in patients with abnormal liver biochemistries, elevated autoantibodies, clinical findings suggestive of portal hypertension, systemic autoimmune or inflammatory diseases, hepatomegaly, cirrhosis by imaging, or other indications. These scenarios present significant diagnostic challenges and are rarely discussed in detail in the literature or textbooks. This article aims to provide a comprehensive review of a group of selected rare liver diseases, with a focus on metabolic, storage and inclusion disorders, that may exhibit a near-normal histology on biopsy. By recognizing subtle histologic features and correlating with clinical history, laboratory results and imaging findings, it is often possible to narrow down the differential diagnosis. In many cases, this integrative approach can yield a definitive diagnosis, allowing for tailored treatment and better patient outcomes.

Although macrophages are armed with potent antibacterial functions, Mycobacterium tuberculosis (Mtb) replicates inside these innate immune cells. Determinants of macrophage intrinsic bacterial control, and the Mtb strategies to overcome them, are poorly understood. To further study these processes, we used an affinity tag purification mass spectrometry (AP-MS) approach to identify 187 Mtb-human protein-protein interactions (PPIs) involving 34 secreted Mtb proteins. This interaction map revealed two factors involved in Mtb pathogenesis-the secreted Mtb protein, LpqN, and its binding partner, the human ubiquitin ligase CBL. We discovered that an lpqN Mtb mutant is attenuated in macrophages, but growth is restored when CBL is removed. Conversely, Cbl^-/- macrophages are resistant to viral infection, indicating that CBL regulates cell-intrinsic polarization between antibacterial and antiviral immunity. Collectively, these findings illustrate the utility of this Mtb-human PPI map for developing a deeper understanding of the intricate interactions between Mtb and its host.