Chronic liver diseases like chronic hepatitis, chronic alcohol abuse or chronic toxic liver disease may cause

- liver failure and hepatorenal syndrome

- fibrosis and cirrhosis of liver

Cirrhosis may also occur in primary biliary cirrhosis. Rarely, cirrhosis is congenital.

Malignant neoplasm of liver and intrahepatic bile ducts. The most frequent forms are metastatic malignant neoplasm of liver)

- liver cell carcinoma

- hepatocellular carcinoma

- hepatoma

- cholangiocarcinoma

- hepatoblastoma

- angiosarcoma of liver

- Kupffer cell sarcoma

- other sarcomas of liver

Benign neoplasm of liver include hepatic hemangiomas, hepatic adenomas, and focal nodular hyperplasia (FNH).

Many imaging modalities are used to aid in the diagnosis of primary liver cancer. For HCC these include sonography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI). When imaging the liver with ultrasound, a mass greater than 2 cm has more than 95% chance of being HCC. The majority of cholangiocarcimas occur in the hilar region of the liver, and often present as bile duct obstruction. If the cause of obstruction is suspected to be malignant, endoscopic retrograde cholangiopancreatography (ERCP), ultrasound, CT, MRI and magnetic resonance cholangiopancreatography (MRCP) are used.

Tumor markers, chemicals sometimes found in the blood of people with cancer, can be helpful in diagnosing and monitoring the course of liver cancers. High levels of alpha-fetoprotein (AFP) in the blood can be found in many cases of HCC and intrahepatic cholangiocarcinoma. Cholangiocarcinoma can be detected with these commonly used tumor markers: carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). These tumour markers are found in primary liver cancers, as well as in other cancers and certain other disorders.

Several different problems may lead to the diagnosis, usually by two years of age:

- seizures or other manifestations of severe fasting hypoglycemia

- hepatomegaly with abdominal protuberance

- hyperventilation and apparent respiratory distress due to metabolic acidosis

- episodes of vomiting due to metabolic acidosis, often precipitated by minor illness and accompanied by hypoglycemia

Once the diagnosis is suspected, the multiplicity of clinical and laboratory features usually makes a strong circumstantial case. If hepatomegaly, fasting hypoglycemia, and poor growth are accompanied by lactic acidosis, hyperuricemia, hypertriglyceridemia, and enlarged kidneys by ultrasound, gsd I is the most likely diagnosis. The differential diagnosis list includes glycogenoses types III and VI, fructose 1,6-bisphosphatase deficiency, and a few other conditions (page 5), but none are likely to produce all of the features of GSD I.

The next step is usually a carefully monitored fast. Hypoglycemia often occurs within six hours. A critical blood specimen obtained at the time of hypoglycemia typically reveals a mild metabolic acidosis, high free fatty acids and beta-hydroxybutyrate, very low insulin levels, and high levels of glucagon, cortisol, and growth hormone. Administration of intramuscular or intravenous glucagon (0.25 to 1 mg, depending on age) or epinephrine produces little rise of blood sugar.

The diagnosis is definitively confirmed by liver biopsy with electron microscopy and assay of glucose-6-phosphatase activity in the tissue and/or specific gene testing, available in recent years.

Prevention of cancers can be separated into primary, secondary, and tertiary prevention. Primary prevention preemptively reduces exposure to a risk factor for liver cancer. One of the most successful primary liver cancer preventions is vaccination against hepatitis B. Vaccination against the hepatitis C virus is currently unavailable. Other forms of primary prevention are aimed at limiting transmission of these viruses by promoting safe injection practices, screening blood donation products, and screening high-risk asymptomatic individuals. Aflatoxin exposure can be avoided by post-harvest intervention to discourage mold, which has been effective in west Africa. Reducing alcohol abuse, obesity, and diabetes would also reduce rates of liver cancer. Diet control in hemochromatosis could decrease the risk of iron overload, decreasing the risk of cancer.

Secondary prevention includes both cure of the agent involved in the formation of cancer (carcinogenesis) and the prevention of carcinogenesis if this is not possible. Cure of virus-infected individuals is not possible, but treatment with antiviral drugs such as interferon can decrease the risk of liver cancer. Chlorophyllin may have potential in reducing the effects of aflatoxin.

Tertiary prevention includes treatments to prevent the recurrence of liver cancer. These include the use of chemotherapy drugs and antiviral drugs.

Without adequate metabolic treatment, patients with GSD I have died in infancy or childhood of overwhelming hypoglycemia and acidosis. Those who survived were stunted in physical growth and delayed in puberty because of chronically low insulin levels. Mental retardation from recurrent, severe hypoglycemia is considered preventable with appropriate treatment.

Hepatic complications have been serious in some patients. Adenomas of the liver can develop in the second decade or later, with a small chance of later malignant transformation to hepatoma or hepatic carcinomas (detectable by alpha-fetoprotein screening). Several children with advanced hepatic complications have improved after liver transplantation.

Additional problems reported in adolescents and adults with GSD I have included hyperuricemic gout, pancreatitis, and chronic renal failure. Despite hyperlipidemia, atherosclerotic complications are uncommon.

With diagnosis before serious harm occurs, prompt reversal of acidotic episodes, and appropriate long-term treatment, most children will be healthy. With exceptions and qualifications, adult health and life span may also be fairly good, although lack of effective treatment before the mid-1970s means information on long-term efficacy is limited.

People get liver cancer (also called "hepatocellular carcinoma, HCC" or "hepatoma)" typically from a prolonged Hepatitis B or C infection or as a result of cirrhosis from chronic alcoholism. Liver cancer may bring about yellowing of the skin and eyes (jaundice), itching (pruritus), or cause a buildup of fluid in the abdomen (ascites). A person may feel an enlarging mass, or the cancer might be revealed by abnormal liver function tests.

An attending practitioner might order a biopsy, an MRI or a CT scan, and a patient might be monitored through blood tests (including alpha-fetoprotein, liver-function tests or ultrasound. These cancers are typically treated according to their TNM stage and whether or not cirrhosis is present. Options include surgical resection, embolisation, ablation or a liver transplant.

Colorectal cancer is a disease of old age: It typically originates in the secretory cells lining the gut, and risk factors include diets low in vegetable fibre and high in fat. If a younger person gets such a cancer, it is often associated with hereditary syndromes like Peutz-Jegher's, hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis. Colorectal cancer can be detected through the bleeding of a polyp, colicky bowel pain, a bowel obstruction or the biopsy of a polyp at a screening colonoscopy. A constant feeling of having to go to the toilet or anemia might also point to this kind of cancer.

Use of a colonoscope can find these cancers, and a biopsy can reveal the extent of the involvement of the bowel wall. Removal of a section of the colon is necessary for treatment, with or without chemotherapy. Colorectal cancer has a comparatively good prognosis when detected early.

Several approaches have been taken to address tumor hypoxia. Some companies tried to develop drugs that are activated in hypoxic environments (Novacea, Inc. Proacta, Inc, and Threshold Pharmaceuticals, Inc), while others are currently seeking to reduce tumor hypoxia (Diffusion Pharmaceuticals, Inc. and NuvOx Pharma, LLC).

Several companies have tried to develop drugs that are activated in hypoxic environments. These drug candidates target levels of hypoxia that are common in tumors but are rare in normal tissues. The hypoxic zones of tumors generally evade traditional chemotherapeutic agents and ultimately contribute to relapse. In the literature, hypoxia has been demonstrated to be associated with a worse prognosis, making it a determinant of cancer progression and therapeutic response. Several review articles summarize the current status of hypoxic cytotoxins (hypoxia activated prodrugs). Companies that have tried drugs that are activated in hypoxic environments included Novacea, Inc. Proacta, and Threshold Pharmaceuticals. Novacea Inc discontinued development of its hypoxia activated drug. Proacta’s drug PR610 failed a Phase I clinical trial due to toxicity. Threshold Pharmaceuticals discontinued the hypxia activated prodrug, TH-302, after Phase III trials failed to show statistically significant overall survival.

Niacinamide, the active form of vitamin B, acts as a chemo- and radio-sensitizing agent by enhancing tumor blood flow, thereby reducing tumor hypoxia. Niacinamide also inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy. As of August 2016, no clinical trials appear to be in progress for this indication.

Another approach to the treatment of tumor hypoxia is the use of an oxygen diffusion-enhancing compound to reoxygenate the hypoxic zones of tumors. The developer of oxygen diffusion-enhancing compounds, Diffusion Pharmaceuticals, tested its lead compound, trans sodium crocetinate (TSC), in a Phase II clinical trial in 59 patients newly diagnosed with glioblastoma multiforme. The results of the Phase II showed that 36% of the full-dose TSC patients were alive at 2 years, compared with historical survival values ranging from 27% to 30% for the standard of care. The main endpoint of the trial was survival at two years, not overall survival.

Another drug in development that is designed to reduce tumor hypoxia is NuvOx Pharma’s NVX-108. NVX-108 is a formulation of the perfluorocarbon, dodecafluoropentane (DDFPe). NVX-108 is injected intravenously, flows through the lungs and picks up oxygen, then flows through the arteries and releases oxygen in the precense of hypoxic tissue. A Phase Ib/II clinical trial is in progress for newly diagnosed glioblastoma multiforme. Early results have shown reversal of tumor hypoxia, and the trial continues to progress.

Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic microenvironements in solid tumors are a result of available oxygen being consumed within 70 to 150 μm of tumour vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism. Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior.